Correlation of MRI Brain Injury Findings with Neonatal Clinical Factors in Infants with Congenital Diaphragmatic Hernia

BACKGROUND AND PURPOSE:Infants with congenital diaphragmatic hernia are reported to have evidence of brain MR imaging abnormalities. Our study aimed to identify perinatal clinical factors in infants with congenital diaphragmatic hernia that are associated with evidence of brain injury on MR imaging performed before hospital discharge.MATERIALS AND METHODS:MRIs performed before hospital discharge in infants with congenital diaphragmatic hernia were scored for brain injury by 2 pediatric neuroradiologists. Perinatal variables and clinical variables from the neonatal intensive care unit stay were analyzed for potential associations with brain MR imaging findings.RESULTS:Fifty-three infants with congenital diaphragmatic hernia (31 boys) were included. At least 1 abnormality was seen on MR imaging in 32 infants (60%). The most common MR imaging findings were enlarged extra-axial spaces (36%), intraventricular hemorrhage (23%), ventriculomegaly (19%), white matter injury (17%), and cerebellar hemorrhage (17%). The MR imaging brain injury score was associated with extracorporeal membrane oxygenation (P = .0001), lack of oral feeding at discharge (P = .012), use of inotropes (P = .027), and gastrostomy tube placement before hospital discharge (P = .024). The MR imaging brain injury score was also associated with a large diaphragmatic defect size (P = .011).CONCLUSIONS:Most infants with congenital diaphragmatic hernia have at least 1 abnormality identified on MR imaging of the brain performed before discharge. The main predictors of brain injury in this population are a requirement for extracorporeal membrane oxygenation, large diaphragmatic defect size, and lack of oral feeding at discharge.

Congenital diaphragmatic hernia (CDH), with an incidence of 1 case per 2000 live births, is an anomaly associated with substantial morbidity and mortality.¹ Survivors of CDH are at risk for long-term respiratory, gastrointestinal, nutritional, hearing, and neurologic sequelae, requiring multidisciplinary support, especially during early childhood.¹ Prenatal predictive factors for increased morbidity and mortality include prenatal imaging findings of liver herniation into the chest, lung to head ratio on prenatal sonography, or lung volumes on fetal MR imaging.^2–4 The size of the diaphragmatic defect is another factor that likely plays a major role in morbidity and mortality in infants with congenital diaphragmatic hernia.⁵ However, the association of the defect size with evidence of injury on brain imaging has not been studied, to our knowledge.Long-term neurodevelopmental and neurobehavioral disabilities are reported in up to 70% of infants with congenital diaphragmatic hernia.^6–9 Both brain maturational delays and evidence of brain injury have been reported on imaging.^8,9 There continues to be some controversy about the correlation of neuroimaging abnormalities in CDH with neurologic outcome. In a small cohort of patients with CDH with prenatal and postnatal imaging, Tracy et al⁹ identified an association between brain injury seen on postnatal CT/MR imaging in 4 infants and neurodevelopmental outcome at 1 year. There was no correlation between prenatal factors and neurodevelopmental outcome in this study.⁹ In another study by Danzer et al,¹⁰ postnatal brain MR imaging abnormalities were associated with lower cognitive scores, motor dysfunction, and language deficits.The impact of extracorporeal membrane oxygenation (ECMO) on neonates with CDH requiring ECMO is of clinical relevance. Studies suggest that neonates with CDH who require ECMO have a greater incidence of adverse neurodevelopmental sequelae, though it unclear whether the severity of the illness leading up to ECMO (hypercapnia, hypotension, and so forth) or the ECMO itself should be implicated.^6,11Which clinical factors in the neonatal intensive care unit play a role in brain injury in infants with CDH is yet to be determined.In this study, we have developed a brain injury score to determine whether brain injury seen on predischarge MRI in infants with CDH is associated with diaphragmatic defect size and postnatal clinical factors in the NICU.     

Apparent Diffusion Coefficient Value Changes and Clinical Correlation in 90 Cases of Cytomegalovirus-Infected Fetuses with Unremarkable Fetal MRI Results

BACKGROUND AND PURPOSE:Cytomegalovirus is the leading intrauterine infection. Fetal MR imaging is an accepted tool for fetal brain evaluation, yet it still lacks the ability to accurately predict the extent of the neurodevelopmental impairment, especially in fetal MR imaging scans with unremarkable findings. Our hypothesis was that intrauterine cytomegalovirus infection causes diffusional changes in fetal brains and that those changes may correlate with the severity of neurodevelopmental deficiencies.MATERIALS AND METHODS:A retrospective analysis was performed on 90 fetal MR imaging scans of cytomegalovirus-infected fetuses with unremarkable results and compared with a matched gestational age control group of 68 fetal head MR imaging scans. ADC values were measured and averaged in the frontal, parietal, occipital, and temporal lobes; basal ganglia; thalamus; and pons. For neurocognitive assessment, the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) was used on 58 children in the cytomegalovirus-infected group.RESULTS:ADC values were reduced for the cytomegalovirus-infected fetuses in most brain areas studied. The VABS-II showed no trend for the major domains or the composite score of the VABS-II for the cytomegalovirus-infected children compared with the healthy population distribution. Some subdomains showed an association between ADC values and VABS-II scores.CONCLUSIONS:Cytomegalovirus infection causes diffuse reduction in ADC values in the fetal brain even in unremarkable fetal MR imaging scans. Cytomegalovirus-infected children with unremarkable fetal MR imaging scans do not deviate from the healthy population in the VABS-II neurocognitive assessment. ADC values were not correlated with VABS-II scores. However, the lack of clinical findings, as seen in most cytomegalovirus-infected fetuses, does not eliminate the possibility of future neurodevelopmental pathology.

Cytomegalovirus (CMV) infection is the most common intrauterine infection, with an overall birth prevalence of 1% (range, 0.2%–2.5%).^1,2 Only 10%–15% of the infected fetuses are symptomatic at birth, presenting with typical clinical findings of congenital infection,^3,4 while an additional 10%–15% of infants develop the symptoms during the first years of life.^1,2,5,6 The clinical findings include, but are not limited to, intrauterine growth restriction, periventricular calcifications, microcephaly, ventriculomegaly, hepatosplenomegaly, and cardiovascular system anomalies.^3,4,7Most symptomatic infants will have long-term sequelae, including neurodevelopmental damage with intellectual disabilities, ranging up to severe decreases in cognitive capacity.^2,4,5,8,9 Asymptomatic neonates constitute most cases, up to 90% of the infected fetuses, with outcomes still unclear due to limited research.^1,5,6,8,9Sonography is a widely used prenatal screening tool and can show typical findings suggestive of CMV infection. Recent studies have shown that sonography is not sensitive enough for the entire spectrum of neuropathologies, mainly brain maturation.^10,11 Fetal head MR imaging (feMRI) is accepted as a complementary test for the evaluation of the brain. Studies have shown that feMRI produces much more information, including improved spatial resolution, visualization of the entire brain parenchyma, and detection of white matter maturation and pathologies earlier and better than sonography.^10–13 However, even with both techniques combined, it is still unclear how to accurately predict the extent of the neurodevelopmental impairment in the prenatal period, especially in cases without any notable imaging pathology.^10,11,13,14Diffusion-weighted imaging (DWI, DTI) was studied extensively for its utility in the evaluation of the normal development of the fetal brain.^15–20 One of the DWI metrics, the apparent diffusion coefficient, allows quantitative evaluation of cerebral maturation and intracellular changes in utero.^15,18–22 Very little research has been done examining the ADC values in CMV-infected fetal brains, and even less research has focused on fetuses with normal feMRI results.^14,18In our current study, we compared ADC values in several anatomic brain areas of CMV-infected fetuses with unremarkable feMRI results and an age-matched control group with normal MR imaging findings. For neurodevelopmental assessment, the Vineland Adaptive Behavior Scales, Second Edition (VABS-II)^23,24 was performed on children from the CMV-infected group.Our hypothesis was that CMV-infection causes diffusional changes in fetal brains and that those changes may be correlated to the severity of neurodevelopmental deficiencies.     

Variability of Forebrain Commissures in Callosal Agenesis: A Prenatal MR Imaging Study

BACKGROUND AND PURPOSE:Agenesis of the corpus callosum, even when isolated, may be characterized by anatomic variability. The aim of this study was to describe the types of other forebrain commissures in a large cohort of randomly enrolled fetuses with apparently isolated agenesis of the corpus callosum at prenatal MR imaging.MATERIALS AND METHODS:All fetuses with apparent isolated agenesis of the corpus callosum undergoing prenatal MR imaging from 2004 to 2014, were evaluated for the presence of the anterior or a vestigial hippocampal commissure assessed in consensus by 2 pediatric neuroradiologists.RESULTS:Overall, 62 cases of agenesis of the corpus callosum were retrieved from our data base. In 3/62 fetuses (4.8%), no forebrain commissure was visible at prenatal MR imaging, 23/62 fetuses (37.1%) presented with only the anterior commissure, and 20/62 fetuses (32.3%) showed both the anterior commissure and a residual vestigial hippocampal commissure, whereas in the remaining 16/62 fetuses (25.8%), a hybrid structure merging a residual vestigial hippocampal commissure and a rudiment of the corpus callosum body was detectable. Postnatal MR imaging, when available, confirmed prenatal forebrain commissure findings.CONCLUSIONS:Most fetuses with apparent isolated agenesis of the corpus callosum showed at least 1 forebrain commissure at prenatal MR imaging, and approximately half of fetuses also had a second commissure: a vestigial hippocampal commissure or a hybrid made of a hippocampal commissure and a rudimentary corpus callosum body. Whether such variability is the result of different genotypes and whether it may have any impact on the long-term neurodevelopmental outcome remains to be assessed.

The corpus callosum (CC) is the major white matter forebrain commissure. Agenesis of the corpus callosum (ACC) is among the most common congenital brain anomalies, often coexisting with chromosomal or genetic syndromes and other malformations of the central nervous system or extra-CNS location,^1–4 which may negatively impact the neurodevelopmental outcome.^5–7 MR imaging^8,9 has been introduced in prenatal assessment of suspected ACC as a complementary investigation to sonography, due to its high performance in evaluating the fetal brain structures and detecting associated anomalies that may be overlooked at sonography but may impact the final outcome.Both prenatal and postnatal MR imaging may accurately depict the brain features accompanying ACC. For example, the presence or absence of Probst bundles has been extensively addressed in the literature.^10–12 On the contrary, the involvement in ACC of the other forebrain commissures, namely the anterior commissure (AC) and the hippocampal commissure (HC), has been poorly investigated and mainly as sporadic imaging reports in the postnatal setting.^8,13 These postnatal reports did not provide consistent data about how the other forebrain commissures are involved in ACC. These reports are not the result of a random case screening; rather, they are a collection of clinical cases.Consistent visualization of the other forebrain commissures seems feasible at prenatal MR imaging, albeit very poor data are available regarding the forebrain commissures in fetuses with ACC.The aim of this study was to describe the types of other forebrain commissures and to assess their frequency in a large cohort of fetuses with apparent isolated ACC on prenatal MR imaging.     

Diagnostic Value of Prenatal MR Imaging in the Detection of Brain Malformations in Fetuses before the 26th Week of Gestational Age

BACKGROUND AND PURPOSE:In several countries, laws and regulations allow abortion for medical reasons within 24–25 weeks of gestational age. We investigated the diagnostic value of prenatal MR imaging for brain malformations within 25 weeks of gestational age.MATERIALS AND METHODS:We retrospectively included fetuses within 25 weeks of gestational age who had undergone both prenatal and postnatal MR imaging of the brain between 2002 and 2014. Two senior pediatric neuroradiologists evaluated prenatal MR imaging examinations blinded to postnatal MR imaging findings. With postnatal MR imaging used as the reference standard, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the prenatal MR imaging in detecting brain malformations.RESULTS:One-hundred nine fetuses (median gestational age at prenatal MR imaging: 22 weeks; range, 21–25 weeks) were included in this study. According to the reference standard, 111 malformations were detected. Prenatal MR imaging failed to detect correctly 11 of the 111 malformations: 3 midline malformations, 5 disorders of cortical development, 2 posterior fossa anomalies, and 1 vascular malformation. Prenatal MR imaging misdiagnosed 3 findings as pathologic in the posterior fossa.CONCLUSIONS:The diagnostic value of prenatal MR imaging between 21 and 25 weeks'' gestational age is very high, with limitations of sensitivity regarding the detection of disorders of cortical development.

Prenatal MR imaging of the brain is a technique increasingly used in clinical practice; it is generally performed as a second-look investigation in case of abnormal or suspicious findings at prenatal ultrasonography (US).¹Prenatal MR imaging is often advocated as an important tool in parental counseling and decision-making regarding the fate of the pregnancy.² In several countries, crucial decisions on pregnancy must be made before the 24th to 25th week of gestation because local laws and regulations allow abortion for medical reasons within this deadline. In these cases, a correct diagnosis should be reached early during pregnancy because performing additional MR imaging follow-up is not compatible with legal time constraints. Moreover, an early correct diagnosis may have an important impact on the psychological well-being of the mother and may help the clinician in planning other diagnostic or therapeutic procedures.To determine prenatal MR imaging accuracy, several studies have already compared its results with ones from postmortem examinations,^3–5 postnatal MR imaging,^6–11 or both postmortem examination and postnatal MR imaging.^12,13 However, these studies were performed in small cohorts of fetuses, and they were focused on a single specific class of anomalies or accounted for few fetuses younger than 24–25 weeks'' gestational age (GA), thus providing little information about the diagnostic accuracy of prenatal MR imaging performed at an early GA.The purpose of our study was to assess the diagnostic value of prenatal MR imaging in the diagnosis of brain malformations, in a large cohort of fetuses (109 cases) within 25 weeks of GA, by using postnatal MR imaging as the reference standard.     

Nonmicrocephalic Infants with Congenital Zika Syndrome Suspected Only after Neuroimaging Evaluation Compared with Those with Microcephaly at Birth and Postnatally: How Large Is the Zika Virus “Iceberg”?

BACKGROUND AND PURPOSE:Although microcephaly is the most prominent feature of congenital Zika syndrome, a spectrum with less severe cases is starting to be recognized. Our aim was to review neuroimaging of infants to detect cases without microcephaly and compare them with those with microcephaly.MATERIALS AND METHODS:We retrospectively evaluated all neuroimaging (MR imaging/CT) of infants 1 year of age or younger. Patients with congenital Zika syndrome were divided into those with microcephaly at birth, postnatal microcephaly, and without microcephaly. Neuroimaging was compared among groups.RESULTS:Among 77 infants, 24.6% had congenital Zika syndrome (11.7% microcephaly at birth, 9.1% postnatal microcephaly, 3.9% without microcephaly). The postnatal microcephaly and without microcephaly groups showed statistically similar imaging findings. The microcephaly at birth compared with the group without microcephaly showed statistically significant differences for the following: reduced brain volume, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, an enlarged extra-axial space, an enlarged cisterna magna (all absent in those without microcephaly), and polymicrogyria (the only malformation present without microcephaly). There was a trend toward pachygyria (absent in groups without microcephaly). The group with microcephaly at birth compared with the group with postnatal microcephaly showed significant differences for simplified gyral pattern, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, and an enlarged extra-axial space.CONCLUSIONS:In microcephaly at birth, except for polymicrogyria, all patients showed abnormalities described in the literature. In postnatal microcephaly, the only abnormalities not seen were a simplified gyral pattern and calcifications outside the cortico-subcortical junction. Infants with normocephaly presented with asymmetric frontal polymicrogyria, calcifications in the cortico-subcortical junction, mild ventriculomegaly, and delayed myelination.

The Zika virus (ZIKV) is an arboviral disease with its main vector being Aedes aegypti.¹ There are also reports of sexual transmission and viral detection in urine² and tears.³ The first epidemic of ZIKV occurred in 2007 in the Yap Islands, Micronesia⁴; the second occurred in 2013, in French Polynesia⁵; and the third began in Bahia, Northeast Brazil, in March 2015.⁶ In August 2015, in Pernambuco, Northeast Brazil, a significant increase in the number of congenital microcephaly cases was reported to the health authorities. Currently, the relationship between the ZIKV and microcephaly is well-established.⁷The most characteristic findings of congenital Zika syndrome (CZS) include microcephaly, arthrogryposis, and ophthalmologic and hearing abnormalities.^8–12 The major neuroimaging abnormalities reported by initial case series^8,13,14 were calcifications in the cortico-subcortical white matter junction and malformations of cortical development, associated with other brain abnormalities.^8,13,14These imaging features were reported on the basis of severe cases of microcephaly identified at birth.^8,13–15 However, some of these patients⁸ did not have microcephaly at birth and were detected because in the beginning, microcephaly was defined as a head circumference of ≤33 cm, a cutoff that decreased 2 times before the establishment of the current criteria based on the Intergrowth-21st.¹⁶ Therefore, there is probably a disease spectrum that has only recently been recognized, with some patients presenting with less severe brain damage and even without microcephaly.We reviewed the brain CT and MR imaging scans of infants 1 year of age or younger, to find cases of CZS without microcephaly and to compare them with infants with microcephaly. We hypothesized that these mild cases of CZS without microcephaly, not suspected before neuroimaging evaluation, have a milder degree of brain damage.     

Brain Development in Fetuses of Mothers with Diabetes: A Case-Control MR Imaging Study

BACKGROUND AND PURPOSE:Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of brain metabolism (¹H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured.MATERIALS AND METHODS:Women with singleton pregnancies with diabetes (n = 26) and healthy controls (n = 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks'' gestation.RESULTS:Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for ¹H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean [SD]) in the fetal brain in women with diabetes compared with controls (1.74 [0.79] versus 1.79 [0.64], P = .81; and 0.78 [0.28] versus 0.94 [0.36], P = .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 [0.11] versus 0.53 [0.10], P = .04). There was no difference in mean [SD] anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 [0.12] versus 1.16 [0.08], P = .96; 1.54 [0.16] versus 1.59 [0.20], P = .56; and 1.49 [0.23] versus 1.52 [0.23], P = .89, respectively) or volume of the cerebrum (243.0 mL [22.7 mL] versus 253.8 mL [31.6 mL], P = .38).CONCLUSIONS:Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted.

Diabetes is the most common medical disorder of pregnancy with the prevalence of type 1 (T1DM), type 2 (T2DM), and gestational diabetes (GDM) all increasing among women of childbearing age in resource-rich settings. The perinatal complications of maternal diabetes, which reflect altered metabolic function in utero, include major congenital malformations, macrosomia, and stillbirth.¹ Long-term, children born to mothers with diabetes are at increased risk for cognitive impairment,^2,3 inattentiveness,⁴ impaired working memory,⁵ and altered language development.⁶ These adverse outcomes are not fully explained by postnatal events; this question focuses research attention on the vulnerability of the developing brain during fetal life. Identification of the nature and timing of alterations to brain structure and function that underlie neurocognitive impairment could help the development of strategies designed to improve the long-term outcome of children of diabetic mothers.During fetal life, the predominant source of brain energy is glucose, which crosses the placenta by facilitated diffusion.⁷ While severe perturbations in glucose homeostasis after birth are associated with neonatal brain injury, the effect of chronic fluctuant glucose concentration experienced by fetuses of women with diabetes on in utero brain development has not been investigated, to our knowledge. Maternal diabetes is also associated with disturbances in fatty acid metabolism: Umbilical venous blood docosahexaenoic acid concentration is reduced; this reduction reflects lower docosahexaenoic acid transfer to the fetus.⁸ Docosahexaenoic acid accumulates in the brain in abundance from the third trimester and is essential for neurogenesis, neurotransmission, and protection from oxidative stress. Reduced bioavailability of this key metabolite has been suggested as a putative mechanism for programming altered neurodevelopment.^8,9Advances in proton MR spectroscopy (¹H-MRS) and diffusion-weighted and structural MR imaging (sMRI) have led to the development of objective and sensitive measures of fetal brain structure and metabolism. Use of these technologies has revealed alterations in the cerebral NAA:choline ratio and gyrification in fetuses with congenital heart disease,¹⁰ temporal lobe volumes in fetuses with congenital cytomegalovirus infection,¹¹ and ADC values and parenchymal volume in antenatal ventriculomegaly.^12,13 Historically, most fetal imaging studies have been undertaken at 1.5T. However, although an increasing number of studies have been performed at 3T field strength,^14–20 which has benefits over 1.5T due to improved signal-to-noise and is likely to be advantageous for depicting fetal anatomy,²¹ to date, there have been no studies assessing the feasibility of recruiting women with diabetes for fetal neuroimaging.Early-life metrics derived from ¹H-MRS, DWI, and sMRI are associated with function in childhood. After preterm birth, NAA/Cho and Cho/Cr ratios are associated with neurodevelopmental outcome at 2 years of age,²² lactate/NAA predicts outcome following hypoxic-ischemic encephalopathy,²³ and abnormalities in the NAA/Cr and Cho/Cr ratios in neonates²⁴ and older children²⁵ predict developmental delay. Increased ADC values in white matter are associated with diffuse white matter injury following preterm birth²⁶ and with poor outcome after hypoxic-ischemic encephalopathy in term infants.^27,28 Finally, reduced regional and whole-brain volumes are associated with specific preterm comorbidities,^29,30 and structural alteration predicts long-term impairment after preterm birth.^31,32On the basis of disturbances to fetal glucose and fatty acid metabolism associated with maternal diabetes and the neurocognitive profile of offspring, we aimed to investigate the feasibility of comprehensive fetal brain assessment by acquiring measurements of NAA/Cho, NAA/Cr, and Cho/Cr ratios; regional apparent diffusion coefficient measurements; and volume of the cerebrum during the third trimester of pregnancy from women with diabetes and from healthy controls by using 3T MR imaging. The secondary aim was to determine normal values for these measures for future studies designed to investigate the effect of maternal disease on fetal brain development and in utero origins of neurodevelopmental impairment.     

Brain Parenchymal Signal Abnormalities Associated with Developmental Venous Anomalies in Children and Young Adults

BACKGROUND AND PURPOSE:Abnormal signal in the drainage territory of developmental venous anomalies has been well described in adults but has been incompletely investigated in children. This study was performed to evaluate the prevalence of brain parenchymal abnormalities subjacent to developmental venous anomalies in children and young adults, correlating with subject age and developmental venous anomaly morphology and location.MATERIALS AND METHODS:Two hundred eighty-five patients with developmental venous anomalies identified on brain MR imaging with contrast, performed from November 2008 through November 2012, composed the study group. Data were collected for the following explanatory variables: subject demographics, developmental venous anomaly location, morphology, and associated parenchymal abnormalities. Associations between these variables and the presence of parenchymal signal abnormalities (response variable) were then determined.RESULTS:Of the 285 subjects identified, 172 met inclusion criteria, and among these subjects, 193 developmental venous anomalies were identified. Twenty-six (13.5%) of the 193 developmental venous anomalies had associated signal-intensity abnormalities in their drainage territory. After excluding developmental venous anomalies with coexisting cavernous malformations, we obtained an adjusted prevalence of 21/181 (11.6%) for associated signal-intensity abnormalities in developmental venous anomalies. Signal-intensity abnormalities were independently associated with younger subject age, cavernous malformations, parenchymal atrophy, and deep venous drainage of developmental venous anomalies.CONCLUSIONS:Signal-intensity abnormalities detectable by standard clinical MR images were identified in 11.6% of consecutively identified developmental venous anomalies. Signal abnormalities are more common in developmental venous anomalies with deep venous drainage, associated cavernous malformation and parenchymal atrophy, and younger subject age. The pathophysiology of these signal-intensity abnormalities remains unclear but may represent effects of delayed myelination and/or alterations in venous flow within the developmental venous anomaly drainage territory.

Developmental venous anomalies (DVAs) are frequently identified on routine MR imaging of the brain with contrast. DVAs are typically considered normal variants of venous development and usually have no associated imaging findings. However, a subset of DVAs has been associated with findings such as cavernous malformations (CMs),^1–3 thrombosis with subsequent venous infarction,^4–8 lobar atrophy,⁹ T2 and FLAIR signal-intensity abnormalities,^9,10 and SWI hypointensities.¹¹ Signal abnormalities can occur in the drainage territory of DVAs and may produce diagnostic uncertainty with regard to the significance and relationship to presenting symptoms. Signal abnormalities on MR imaging have been described in 12.5%¹⁰ to 28.3%⁹ of DVAs in adults, with an increasing prevalence with older age. While well described in adults, this relationship has not been investigated in children, to our knowledge. The MR imaging appearance of the brain in children is quite different from that in adults during myelination, and the effect of DVAs on regional brain maturation has not been studied.The most commonly proposed etiologies for parenchymal abnormalities associated with DVAs are chronic venous hypertension/insufficiency leading to ischemia or microhemorrhage.^9–12 Although the effect of brain maturation is unknown, on the basis of these pathophysiologic mechanisms, we hypothesized that parenchymal abnormalities would be less common in children compared with adults. This study was performed to test this hypothesis and to investigate clinical factors and DVA characteristics associated with parenchymal signal abnormalities in children and young adults.     

Diagnostic Performance of Ultrafast Brain MRI for Evaluation of Abusive Head Trauma

BACKGROUND AND PURPOSE:MR imaging with sedation is commonly used to detect intracranial traumatic pathology in the pediatric population. Our purpose was to compare nonsedated ultrafast MR imaging, noncontrast head CT, and standard MR imaging for the detection of intracranial trauma in patients with potential abusive head trauma.MATERIALS AND METHODS:A prospective study was performed in 24 pediatric patients who were evaluated for potential abusive head trauma. All patients received noncontrast head CT, ultrafast brain MR imaging without sedation, and standard MR imaging with general anesthesia or an immobilizer, sequentially. Two pediatric neuroradiologists independently reviewed each technique blinded to other modalities for intracranial trauma. We performed interreader agreement and consensus interpretation for standard MR imaging as the criterion standard. Diagnostic accuracy was calculated for ultrafast MR imaging, noncontrast head CT, and combined ultrafast MR imaging and noncontrast head CT.RESULTS:Interreader agreement was moderate for ultrafast MR imaging (κ = 0.42), substantial for noncontrast head CT (κ = 0.63), and nearly perfect for standard MR imaging (κ = 0.86). Forty-two percent of patients had discrepancies between ultrafast MR imaging and standard MR imaging, which included detection of subarachnoid hemorrhage and subdural hemorrhage. Sensitivity, specificity, and positive and negative predictive values were obtained for any traumatic pathology for each examination: ultrafast MR imaging (50%, 100%, 100%, 31%), noncontrast head CT (25%, 100%, 100%, 21%), and a combination of ultrafast MR imaging and noncontrast head CT (60%, 100%, 100%, 33%). Ultrafast MR imaging was more sensitive than noncontrast head CT for the detection of intraparenchymal hemorrhage (P = .03), and the combination of ultrafast MR imaging and noncontrast head CT was more sensitive than noncontrast head CT alone for intracranial trauma (P = .02).CONCLUSIONS:In abusive head trauma, ultrafast MR imaging, even combined with noncontrast head CT, demonstrated low sensitivity compared with standard MR imaging for intracranial traumatic pathology, which may limit its utility in this patient population.

The incidence of abusive head trauma (AHT) in the United States from 2000 to 2009 was 39.8 per 100,000 children younger than 1 year of age and 6.8 per 100,000 children 1 year of age.¹ The outcomes of patients with AHT are worse than those of children with accidental traumatic brain injury, including higher rates of mortality and permanent disability from neurologic impairment.^2–5 The diagnosis of AHT is frequently not recognized when affected patients initially present to a physician, and up to 28% of children with a missed AHT diagnosis may be re-injured, leading to permanent neurologic damage or even death.⁶ Because neuroimaging plays a central role in AHT, continued improvement in neuroimaging is necessary.Common neuroimaging findings of AHT include intracranial hemorrhage, ischemia, axonal injury, and skull fracture, with advantages and disadvantages for both CT and MR imaging for the detection of AHT.⁷ A noncontrast head CT (nHCT) is usually the initial imaging study in suspected AHT due to its high sensitivity for the detection of acute hemorrhage and fracture and the high level of accessibility from the emergency department, and it can be performed quickly and safely without the need for special monitoring equipment.^8,9 The disadvantages of CT include ionizing radiation, particularly in children, and the reduced sensitivity in detecting microhemorrhages, axonal injury, and acute ischemia compared with MR imaging.¹⁰MR imaging is frequently performed in AHT and adds additional information in 25% of all children with abnormal findings on the initial CT scan.¹¹ Brain MR imaging can also be useful for identifying bridging vein thrombosis, differentiating subdural fluid collections from enlarged subarachnoid spaces, characterizing the signal of subdural blood, and demonstrating membrane formation within subdural collections.^12–16 Brain MR imaging findings have correlated with poor outcomes associated with findings on diffusion-weighted imaging and susceptibility-weighted imaging in AHT; however, disadvantages of MR imaging continue to include the need for sedation in children and compatible monitoring equipment.^17–22 Although there is greater accessibility of CT compared with MR imaging, the availability of MR imaging is relatively high and imaging techniques that allow neuroimaging in patients with potential AHT without sedation would be valuable, particularly given the potential adverse effects of sedation on the developing brain.^23,24A potential solution for diagnostic-quality brain MR imaging without sedation in AHT is the use of ultrafast MR imaging (ufMRI) sequences, also termed “fast MR imaging,” “quick MR imaging,” or “rapid MR imaging.” Ultrafast MR imaging uses pulse sequences that rapidly acquire images, potentially reducing motion artifacts and the need for sedation. ufMRI has been most commonly used in pediatric neuroradiology for the evaluation of intracranial shunts in children with hydrocephalus, and most of the reported ufMRI brain protocols include only multiplanar T2-weighted HASTE sequences.^25–34 Consequently, previously reported limitations of ufMRI in detecting intracranial hemorrhage is primarily due to the lack of blood sensitive sequences.³⁵Recently, an ufMRI protocol incorporating sequences in addition to T2 sequences has been reported in pediatric patients with trauma.³⁶ This study did not compare findings with those of a standard MR imaging (stMRI) and included a wider age range of pediatric patients, so the value of ufMRI in pediatric abusive head trauma remains uncertain.³⁶ Therefore, the purpose of our study was to evaluate an ufMRI brain protocol performed without sedation for feasibility in terms of scanning time and diagnostic value as well as diagnostic accuracy compared with nHCT and stMRI of the brain for the detection of intracranial traumatic pathology in patients with suspected AHT.     

Validation of an MRI Brain Injury and Growth Scoring System in Very Preterm Infants Scanned at 29- to 35-Week Postmenstrual Age

BACKGROUND AND PURPOSE:The diagnostic and prognostic potential of brain MR imaging before term-equivalent age is limited until valid MR imaging scoring systems are available. This study aimed to validate an MR imaging scoring system of brain injury and impaired growth for use at 29 to 35 weeks postmenstrual age in infants born at <31 weeks gestational age.MATERIALS AND METHODS:Eighty-three infants in a prospective cohort study underwent early 3T MR imaging between 29 and 35 weeks'' postmenstrual age (mean, 32⁺² ± 1⁺³ weeks; 49 males, born at median gestation of 28⁺⁴ weeks; range, 23⁺⁶–30⁺⁶ weeks; mean birthweight, 1068 ± 312 g). Seventy-seven infants had a second MR scan at term-equivalent age (mean, 40⁺⁶ ± 1⁺³ weeks). Structural images were scored using a modified scoring system which generated WM, cortical gray matter, deep gray matter, cerebellar, and global scores. Outcome at 12-months corrected age (mean, 12 months 4 days ± 1⁺² weeks) consisted of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley III), and the Neuro-Sensory Motor Developmental Assessment.RESULTS:Early MR imaging global, WM, and deep gray matter scores were negatively associated with Bayley III motor (regression coefficient for global score β = −1.31; 95% CI, −2.39 to −0.23; P = .02), cognitive (β = −1.52; 95% CI, −2.39 to −0.65; P < .01) and the Neuro-Sensory Motor Developmental Assessment outcomes (β = −1.73; 95% CI, −3.19 to −0.28; P = .02). Early MR imaging cerebellar scores were negatively associated with the Neuro-Sensory Motor Developmental Assessment (β = −5.99; 95% CI, −11.82 to −0.16; P = .04). Results were reconfirmed at term-equivalent-age MR imaging.CONCLUSIONS:This clinically accessible MR imaging scoring system is valid for use at 29 to 35 weeks postmenstrual age in infants born very preterm. It enables identification of infants at risk of adverse outcomes before the current standard of term-equivalent age.

Preterm infants are at risk of brain injury and impaired brain growth and consequently poorer outcomes in infancy and childhood.^1–6 Scoring of structural MR imaging to classify brain injury and growth has been validated for use at term-equivalent age (TEA) in infants born preterm.^1,7 Initial systems were qualitative, focusing on classification of the severity of WM and cortical gray matter (CGM) injuries.^7–9 The degree of WM abnormality demonstrated significant associations with concurrent motor, neurologic, and neurobehavioral performance^10–13 and increasing WM abnormality was associated with poorer motor and cognitive outcomes.^{1,2,5,7,14–16}Scoring systems of MR imaging at TEA were further developed to include quantitative biometrics to measure the impact of secondary brain maturation and growth following preterm brain injury.¹⁷ These brain metrics correlated with brain volumes and differentiated preterm and term-born infants at TEA MR imaging.¹⁷ At TEA, transcerebellar diameter was associated with fidgety general movements at 3-month corrected age (CA),¹⁸ poorer cognitive outcomes at 12-month CA,¹⁹ and poorer motor and cognitive outcomes at 2-year CA.²⁰ Reduced deep gray matter area at TEA was associated with poorer motor and cognitive outcomes,¹⁹ and an increased interhemispheric distance independently predicted poorer cognitive development at 2-year CA.³ Reduced biparietal width at TEA predicted both motor and cognitive outcomes at 2-year CA in infants born very preterm.^3,21Term-equivalent age MR imaging scoring systems have been further developed to include evaluation of deep gray matter (DGM) structures and the cerebellum.²² At TEA, global brain abnormality scores were significantly associated with motor outcomes at 2-years CA²³; and cognitive outcomes, at 7 years.^24,25 Deep gray matter scores were significantly associated with poorer attention and processing speeds, memory, and learning.^24,25With safe earlier MR imaging now possible with MR compatible incubators, valid scoring systems for use earlier than TEA are required. The aim of this study was to validate an MR imaging scoring system previously developed for very preterm infants at TEA in a cohort of infants born <31-weeks gestational age with MR imaging between 29 and 35 weeks'' postmenstrual age (PMA).²² The study aimed to establish predictive validity for motor and cognitive outcomes at 12-months CA. Secondary aims were to examine inter- and intrarater reproducibility and to examine relationships between global brain abnormality categories and known perinatal risk factors. It was hypothesized that the scoring system would be valid and reliable for use at this earlier time point but with more infants classified with brain abnormalities, due to immaturity rather than injury.     

Phase White Matter Signal Abnormalities in Patients with Clinically Isolated Syndrome and Other Neurologic Disorders

BACKGROUND AND PURPOSE:Identifying MRI biomarkers that can differentiate multiple sclerosis patients from other neurological disorders is a subject of intense research. Our aim was to investigate phase WM signal abnormalities for their presence, prevalence, location, and diagnostic value among patients with clinically isolated syndrome and other neurologic disorders and age-, sex-, and group-matched healthy controls.MATERIALS AND METHODS:Forty-eight patients with clinically isolated syndrome and 30 patients with other neurologic diseases and a healthy control group (n = 47) were included in the study. Subjects were scanned at 3T by using SWI-filtered phase and T2WI, with WM signal abnormalities ≥3 mm being classified.RESULTS:Patients with clinically isolated syndrome had significantly more phase and T2 WM signal abnormalities than healthy controls (P < .001). Phase WM signal abnormalities were more prevalent among patients with clinically isolated syndrome compared with patients with other neurologic disorders (4:1 ratio), whereas T2 WM signal abnormalities were more ubiquitous with a 2:1 ratio. The presence of phase WM signal abnormalities was sensitive for clinically isolated syndrome (70.8%) and achieved a moderate-to-high specificity for differentiating patients with clinically isolated syndrome and healthy controls, patients with other neurologic disorders, and patients with other neurologic disorders of other autoimmune origin (specificity, 70%–76.7%). Combining the presence of ≥2 phase lesions with the McDonald 2005 and 2010 criteria for dissemination in space improved the specificity (90%), but not the accuracy, in differentiating patients with clinically isolated syndrome from those with other neurologic disorders. In subanalyses among patients with clinically isolated syndrome who converted to clinically definite multiple sclerosis versus those who did not within a 3-year follow-up period, converters had significantly more phase (P = .008) but not T2 or T1 WM signal abnormalities.CONCLUSIONS:Phase WM signal abnormalities are prevalent among patients with clinically isolated syndrome. The presence of (multiple) phase WM signal abnormalities tended to be more predictive of conversion to clinically definite multiple sclerosis and was specific in differentiating patients with clinically isolated syndrome and other neurologic disorders, compared with T2 WM signal abnormalities; however, the accuracy remains similar to that of the current McDonald criteria.

The occurrence of WM signal abnormalities (SAs) is a hallmark feature of multiple sclerosis, yet the clinical relevance of the pathologic substrate of WM-SAs is disappointing.^1–4 WM-SAs observed on T2WI and T1WI represent focal pathology and are thought to be caused by inflammation, edema, demyelination, or gliosis.² They are usually secondary to active inflammation, imaged by using postcontrast T1WI gadolinium-enhanced scanning.⁵ Even though T2 WM-SAs are present at the first demyelinating episode, the poor specificity of conventional MR imaging^1,6 and comparable MR imaging features at disease onset compared with ischemic, autoimmune diseases or aging limits their predictive value.Previously, differential diagnosis between MS and other conditions was considered by using brain and spinal cord MR imaging and incorporating number, location, and morphology of T2 WM-SAs in the diagnostic criteria of MS⁷ or by using different nonconventional MR imaging techniques.^6,8–10 It is important to further investigate the value of nonconventional MR imaging techniques in the MS differential diagnosis, for example by using SWI-filtered phase to identify early focal brain pathology indicative of MS, especially in patients with clinically isolated syndrome (CIS).Recent studies have confirmed histologically that WM-SAs visible on MR imaging phase and R^2* correspond to focal iron deposits, whereas T2 and T1 WM-SAs are influenced by water content.¹¹ A substantial subset of MS WM-SAs has phase shifts^11,12 and morphologic differences.^11–15 However, factors other than nonheme iron may influence the observed WM-SA signal, such as changes in myelin, deoxyhemoglobin, and inflammation.^11,16–19 Therefore, because there are a multitude of effects, it is not fully known to what extent they each individually influence SWI-filtered phase changes.Phase changes may signal early WM-SA development^17,20 in that these phase WM-SAs may appear initially but then disappear as the pathology advances.¹⁷ Considering that the distinct pathologies influencing phase shift (eg, cellular/myelin destruction, iron levels, microstructural changes) in WM-SAs are most likely intricately related and are observed in MS and related disorders,^{12,14,15,21–23} the inquiry into pathology visible on SWI-filtered phase remains important regardless of the causative factors.SWI-filtered phase work has mostly focused on patients with MS,^{11,13–15,24} high-field-strength imaging,^11,13,24 or histologically validating phase WM-SAs.^11,25 Regardless of what pathology phase WM-SAs represent, it is imperative to identify whether their presence has diagnostic value. In the present study, we assessed WM-SAs visible on T2WI and SWI-filtered phase among patients with CIS and patients with other neurologic disorders (OND) to investigate their prevalence, location, and ability to differentiate disease groups.     

Brain Changes in Kallmann Syndrome

BACKGROUND AND PURPOSE:Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses.MATERIALS AND METHODS:Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm²). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library.RESULTS:Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus.CONCLUSIONS:This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

Kallmann syndrome (KS) is a rare inherited disorder (affecting about 1 in 10,000 males),¹ clinically characterized by the association of hypogonadotropic hypogonadism and hypo-/anosmia.² Both KS clinical hallmarks derive from a disturbed intrauterine migration process involving olfactory axons and gonadotropin-releasing hormone neurons from the olfactory placode to the hypothalamus.^3,4 The failure of the migration process results in hypo-/aplasia of the rhinencephalon (olfactory bulbs and tracts)^3–6 and in altered gonadotropic axis function with low levels of sex hormones. Besides rhinencephalon abnormalities, distinctive KS neuroradiologic changes have been detected in the brain and bone structures of the anterior cranial fossa by conventional MR imaging^7–14 and CT studies.¹⁵ The most known morphologic brain feature is the reduction in depth and length of the olfactory sulcus, which typically turns medially, opening anteriorly into the interhemispheric fissure.^7–13 This sulcal abnormality is thought to be driven by the absence/hypoplasia of the olfactory bulbs and represents an intriguing model of genetically driven developmental brain abnormalities. Furthermore, a few case reports postulated the strict relationship between KS and midline brain abnormalities, such as corpus callosum agenesis and holoprosencephaly,^6,16 though pathologic and neuroimaging data are relatively scarce and often contradictory.⁷In 2008, a pioneering study by voxel-based morphometry (VBM) MR imaging analysis revealed distinct regional gray and white matter volume changes in male patients with KS outside the frontal orbital regions.¹⁷ No study so far has replicated a larger sample of these findings, which would imply a much more profound effect of KS-related genes (KAL1, FGFR1, PROK2, PROKR2, FGF8, NELF, etc.)¹⁸ and/or sex hormone deficiency on brain morphogenesis and development. Moreover, no study has investigated regional white matter changes revealed by VBM by diffusion tensor imaging, a powerful quantitative technique able to investigate the structural nature of white matter involvement. Finally, novel MR imaging–based analyses have been developed that allow assessing precise curvature, sulcation, and cortical thickness quantitative evaluations,^19–21 thus providing further insights into cortex developmental abnormalities. Such analyses have not been applied to KS, though they might represent useful tools for investigating the structural underpinnings of neurologic and psychiatric disorders anecdotally reported in patients with KS.^22,23By conventional MR imaging and novel quantitative sulcation, curvature, cortical thickness, and tract-based spatial statistics (TBSS) analyses, we aimed to feature, more precisely and in a large sample of male patients, the morphologic and structural brain involvement in KS.     

Ultra-High-Field MR Imaging in Polymicrogyria and Epilepsy

BACKGROUND AND PURPOSE:Polymicrogyria is a malformation of cortical development that is often identified in children with epilepsy or delayed development. We investigated in vivo the potential of 7T imaging in characterizing polymicrogyria to determine whether additional features could be identified.MATERIALS AND METHODS:Ten adult patients with polymicrogyria previously diagnosed by using 3T MR imaging underwent additional imaging at 7T. We assessed polymicrogyria according to topographic pattern, extent, symmetry, and morphology. Additional imaging sequences at 7T included 3D T2* susceptibility-weighted angiography and 2D tissue border enhancement FSE inversion recovery. Minimum intensity projections were used to assess the potential of the susceptibility-weighted angiography sequence for depiction of cerebral veins.RESULTS:At 7T, we observed perisylvian polymicrogyria that was bilateral in 6 patients, unilateral in 3, and diffuse in 1. Four of the 6 bilateral abnormalities had been considered unilateral at 3T. While 3T imaging revealed 2 morphologic categories (coarse, delicate), 7T susceptibility-weighted angiography images disclosed a uniform ribbonlike pattern. Susceptibility-weighted angiography revealed numerous dilated superficial veins in all polymicrogyric areas. Tissue border enhancement imaging depicted a hypointense line corresponding to the gray-white interface, providing a high definition of the borders and, thereby, improving detection of the polymicrogyric cortex.CONCLUSIONS:7T imaging reveals more anatomic details of polymicrogyria compared with 3T conventional sequences, with potential implications for diagnosis, genetic studies, and surgical treatment of associated epilepsy. Abnormalities of cortical veins may suggest a role for vascular dysgenesis in pathogenesis.

Polymicrogyria is a malformation of the cerebral cortex secondary to abnormal migration and postmigrational development.¹ It is characterized by an excessive number of abnormally small gyri separated by shallow sulci, associated with fusion of the overlying molecular layer (layer 1) of the cerebral cortex.² This combination of features produces a characteristic appearance of irregularity at both the cortical surface and cortical–white matter junction.^3,4 Its pathogenesis is still poorly understood, and its histopathology, clinical features, topographic distribution, and imaging appearance are heterogeneous. Deficiencies in the understanding of this malformation result from both causal heterogeneity (causative factors include destructive events such as congenital infections,^5,6 in utero ischemia,⁷ metabolic disorders, and several gene mutations and copy number variations^1,8,9) and the limited number of postmortem examinations available.The topographic distribution of polymicrogyria may be focal, multifocal, or diffuse; unilateral or bilateral; and symmetric or asymmetric.^10–15 Polymicrogyria can occur as an isolated disorder or can be associated with other brain abnormalities such as corpus callosum dysgenesis, cerebellar hypoplasia, schizencephaly, and periventricular and subcortical heterotopia.^16,17Clinical manifestations of patients with polymicrogyria have a large spectrum, ranging from isolated selective impairment of cognitive function¹⁸ to severe encephalopathy and intractable epilepsy.¹⁹ The severity of neurologic manifestations and the age at presentation are, in part, influenced by the extent and location of the cortical malformation but may also depend on its specific etiology.Neuroimaging has a primary role in the diagnosis and classification of polymicrogyria due to its noninvasive nature. Imaging findings are variable and are primarily determined by the morphology of the malformed cortex itself but also by the maturity of myelination and imaging-related technical factors (section thickness, gray-white matter contrast).²⁰ In addition, polymicrogyria-like patterns can be seen in certain malformations, such as tubulinopathies²¹ and cobblestone malformations^22–24; these have different histologic appearances but similar MR imaging appearances to polymicrogyria, which can lead to false diagnoses.On the basis of morphologic characteristics, Barkovich^2,20 described the variable appearance of polymicrogyria on MR imaging and suggested that the gyral-sulcal dysmorphisms may be roughly divided into 3 main categories: coarse with a thick, bumpy cortex and irregular surface on both the pial and gray-white junction sides; delicate with multiple small, fine gyri of thin cortex that remains thin even after myelination; and sawtooth, composed of thin microgyri separated by deep sulci (primarily seen in diffuse polymicrogyria and before myelination develops). However, numerous gradations of morphology exist within these groups. To date, neither functional nor etiologic associations have been inferred on the basis of this imaging categorization of a polymicrogyric cortex.Over the past several years, ultra-high-field 7T MR imaging has been available for in vivo human brain imaging. In vivo 7T MR imaging can provide greater tissue-type identification than that obtained in vitro without stains.²⁵ As a result of an increased signal-to-noise ratio, enhanced image contrast, and improved resolution, MR imaging at 7T can visualize small anatomic structures not previously appreciated at lower fields.^25–28 Because 7T MR imaging has already provided diagnostic benefits in different pathologies²⁸ such as multiple sclerosis,²⁹ cerebrovascular diseases (strokes, microbleeds),^30,31 aneurysms,³² cavernous malformations,³³ brain tumors,³⁴ and degenerative brain diseases like dementia and Parkinson disease,^35,36 we tested the added value of 7T MR imaging in providing details of structural changes and their extent in 10 patients with polymicrogyria with respect to conventional 3T imaging. We also addressed the limitations we encountered while exploring the polymicrogyric brain with 7T.     

Autoimmune Comorbidities Are Associated with Brain Injury in Multiple Sclerosis

BACKGROUND AND PURPOSE:The effect of comorbidities on disease severity in MS has not been extensively characterized. We determined the association of comorbidities with MR imaging disease severity outcomes in MS.MATERIALS AND METHODS:Demographic and clinical history of 9 autoimmune comorbidities confirmed by retrospective chart review and quantitative MR imaging data were obtained in 815 patients with MS. The patients were categorized on the basis of the presence/absence of total and specific comorbidities. We analyzed the MR imaging findings, adjusting for key covariates and correcting for multiple comparisons.RESULTS:Two hundred forty-one (29.6%) study subjects presented with comorbidities. Thyroid disease had the highest frequency (n = 97, 11.9%), followed by asthma (n = 41, 5%), type 2 diabetes mellitus (n = 40, 4.9%), psoriasis (n = 33, 4%), and rheumatoid arthritis (n = 22, 2.7%). Patients with MS with comorbidities showed decreased whole-brain and cortical volumes (P < .001), gray matter volume and magnetization transfer ratio of normal-appearing brain tissue (P < .01), and magnetization transfer ratio of gray matter (P < .05). Psoriasis, thyroid disease, and type 2 diabetes mellitus comorbidities were associated with decreased whole-brain, cortical, and gray matter volumes (P < .05). Psoriasis was associated with a decreased magnetization transfer ratio of normal-appearing brain tissue (P < .05), while type 2 diabetes mellitus was associated with increased mean diffusivity (P < .01).CONCLUSIONS:The presence of comorbidities in patients with MS is associated with brain injury on MR imaging. Psoriasis, thyroid disease, and type 2 diabetes mellitus comorbidities were associated with more severe nonconventional MR imaging outcomes.

MS is a chronic immune-mediated disorder that affects the CNS and is characterized by specific clinical and MR imaging findings.¹ Studies have suggested genetic, environmental, and infectious agents as interacting factors influencing the risk for development of MS.^2,3Epidemiologic evidence from the North American Research Committee on Multiple Sclerosis, the large registry containing patient self-reported data, suggests an increased risk for disability progression in individuals with MS who have additional comorbidities.⁴ An increased prevalence of autoimmune- and nonimmune-mediated comorbidities was reported in patients with MS compared with the general population.^5–14 Examples of the most frequent comorbidities or secondary disorders that co-occur with MS include thyroid disease, rheumatoid arthritis, psoriasis, cardiovascular disorders, depression and anxiety, diabetes mellitus, chronic lung disease, and irritable bowel syndrome, among others.^{4–6,8–10,14,15} The pathogenesis of these associations with MS is unclear at this time but may be linked to a genetic predisposition,^5,16,17 the presence of a chronic inflammatory condition,¹⁰ environmental factors,¹⁸ and the use of disease-modifying therapy.¹⁹It has been postulated that CD4+ T-cells of the Th1 phenotype, CD8+ T-cells, and B-cells play a key role in focal and diffuse destruction of the CNS in patients with MS.²⁰ The immune deviation of CD 4+ T-cells into Th1 and Th2 phenotypes has been the subject of many immunologic and epidemiologic studies in MS.^21,22 In particular, it has been reported that Th1 responses associated with autoimmunity may be attenuated by a Th2 shift.¹³ Several studies reported a positive association of comorbidities in patients with MS when explored from the Th1/Th2 point of view.^13,22,23 However, some other studies suggested that these associations were related more to a demographic selection bias than a true sharing of immunologic and pathologic processes.¹⁴Conventional MR imaging examines visible focal inflammatory changes within the CNS. However, it does not capture the true extent of diffuse GM and WM pathology that is mostly undetected in patients with MS and responsible for long-term development of disability progression.²⁴ On the other hand, nonconventional MR imaging techniques are more sensitive biomarkers for measuring these nonfocal pathologic processes associated with tissue damage in the GM and WM and that are better associated with disease severity.²⁴ Some of these techniques include measures of brain atrophy, magnetization transfer imaging, DWI and DTI, MR spectroscopy, and functional MR imaging.It has been shown that patients with MS with ≥1 cardiovascular risk factor have increased lesion burden and more advanced brain atrophy on MR imaging.^25,26 However, it is not clear whether the presence of other comorbidities may also influence the severity of conventional and nonconventional MR imaging measures in patients with MS. Therefore, in this large-cohort MS study, we aimed to investigate the impact of autoimmune comorbidities on the severity of conventional and nonconventional MR imaging outcomes in patients with MS.     

Diagnostic Performance of a 10-Minute Gadolinium-Enhanced Brain MRI Protocol Compared with the Standard Clinical Protocol for Detection of Intracranial Enhancing Lesions

BACKGROUND AND PURPOSE:The development of new MR imaging scanners with stronger gradients and improvement in coil technology, allied with emerging fast imaging techniques, has allowed a substantial reduction in MR imaging scan times. Our goal was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol with accelerated sequences and to evaluate its diagnostic performance compared with the standard clinical protocol.MATERIALS AND METHODS:Fifty-three patients referred for brain MR imaging with contrast were scanned with a 3T scanner. Each MR image consisted of 5 basic fast precontrast sequences plus standard and accelerated versions of the same postcontrast T1WI sequences. Two neuroradiologists assessed the image quality and the final diagnosis for each set of postcontrast sequences and compared their performances.RESULTS:The acquisition time of the combined accelerated pre- and postcontrast sequences was 10 minutes and 15 seconds; and of the fast postcontrast sequences, 3 minutes and 36 seconds, 46% of the standard sequences. The 10-minute postcontrast axial T1WI had fewer image artifacts (P < .001) and better overall diagnostic quality (P < .001). Although the 10-minute MPRAGE sequence showed a tendency to have more artifacts than the standard sequence (P = .08), the overall diagnostic quality was similar (P = .66). Moreover, there was no statistically significant difference in the diagnostic performance between the protocols. The sensitivity, specificity, and accuracy values for the 10-minute protocol were 100.0%, 88.9%, and 98.1%.CONCLUSIONS:The 10-minute brain MR imaging protocol with contrast is comparable in diagnostic performance with the standard protocol in an inpatient motion-prone population, with the additional benefits of reducing acquisition times and image artifacts.

The prolonged acquisition time of MR imaging is uncomfortable for patients, introduces the potential for motion-related artifacts (especially in critically ill patients), limits clinical availability, and increases cost. Consequently, in the past decade, there has been a concerted effort to develop fast and ultrafast MR imaging protocols.^1–7For many years, continual development of new scanners with stronger gradients and the improvement of coil technology,^8–10 allied with a number of emerging fast imaging techniques, has allowed substantial reduction in MR imaging scan times.^1,11–13 More recently, the development of parallel imaging, a robust method for accelerating MR imaging data acquisitions based on obtaining simultaneous information from arrays of coils, allowing decreased filling of k-space lines, has been the preferred method for decreasing acquisition times.^14–16This study is in accord with recent effort within the neuroradiology research community to accelerate the clinical MR imaging studies and expands on a 5-minute noncontrast brain MR imaging protocol previously validated by our group.¹¹ We previously demonstrated similar image quality and diagnostic accuracy of a 5-minute brain MR imaging protocol compared with the conventional protocol in a motion-prone clinical population. The aim of this study was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol with accelerated sequences and to evaluate its diagnostic performance compared with a standard clinical protocol in a similar clinical population.     

Spectrum of Spinal Cord,Spinal Root,and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis

BACKGROUND AND PURPOSE:Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis.MATERIALS AND METHODS:Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups.RESULTS:At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis (P = .018).CONCLUSIONS:Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent.

The Zika virus infection is transmitted by a bite from an infected mosquito, with Aedes aegypti being the main vector.¹ Zika virus was first discovered in 1947 in monkeys in the Zika forest in Uganda,² and human infection was identified in 1952.³ The first epidemic of Zika virus occurred only in 2007 in Micronesia and the Yap Islands.⁴ The second epidemic was found in 2013, in French Polynesia,⁵ and the third began in Brazil,^6,7 where it was initially detected in Bahia, Northeast Brazil, in March 2015.^6,8In September 2015, a substantial increase in the incidence of infants with microcephaly was detected in northeast Brazil.⁸ For the first time, a strong increase of evidence suggested the association between the Zika virus infection outbreak and microcephaly by congenital infection.⁹ In Brazil, on December 31, 2016, there were 2366 cases of microcephaly and other central nervous system malformations suggestive of congenital Zika syndrome.¹⁰ There are 2 major lineages of Zika virus, the African, reported recently in Guinea-Bissau, and the Asian, reported from Asia and the West Pacific region to the Americas and Cabo Verde, which is the strain currently in Brazil.¹⁰ Neurologic complications have been related only to the Asian strains after 2007.¹⁰ The explanation as to why and how the Brazilian Zika virus strain could have developed this neurotropism for the central nervous system is still unknown.The disease has already spread and, according to the World Health Organization, 76 countries and territories, particularly in Latin America, have reported evidence of transmission of the Zika virus by mosquitoes. Cases of microcephalic infants have been reported in 29 countries.¹⁰In addition to microcephaly, other serious brain abnormalities were observed, especially brain calcifications, predominantly in the cortical and subcortical white matter junction, associated with malformations of cortical development (often polymicrogyria or pachygyria with predominant frontal lobe involvement) and a simplified cortical gyral pattern. Other frequent imaging findings are ventriculomegaly; decrease in brain, brain stem, and cerebellar volumes; enlargement of the cisterna magna and the extra-axial subarachnoid space; corpus callosum abnormalities (hypogenesis and hypoplasia); and delayed myelination.¹¹The congenital Zika syndrome is an entity without a well-known clinical spectrum, probably with only the most severe cases of the spectrum recognized. Other malformations have been described in some infants, such as ophthalmologic alterations^12,13 and arthrogryposis.^11,13,14 Currently, 8% of the children with presumed congenital Zika virus infection followed by the Association for Assistance of Disabled Children (AACD) in Recife, Brazil have arthrogryposis. Among the children with CSF immunoglobulin M (IgM) who tested positive for Zika virus, 6.6% have arthrogryposis.Arthrogryposis multiplex congenita, often known simply as arthrogryposis, is a syndrome characterized by joint contractures, present since birth, affecting ≥2 areas of the body.^15–20 These joint malformations can be attributed to different disorders, such as defects of uterine environment, disorders of connective tissues, muscular dystrophies, and other abnormalities or conditions that affect the central or peripheral nervous systems in at least one of the components of the motor pathways from the spinal cord to muscles.^16,18 Regardless of the cause, children affected by arthrogryposis have onset and severe weakness early in intrauterine life, with immobilization of joints at different developmental stages.¹⁶No study has yet analyzed qualitatively and quantitatively MR imaging of the spinal cord of children with congenital Zika syndrome, to our knowledge. Because there is a spectrum of congenital Zika syndrome for brain abnormalities, a similar spectrum might occur in the spinal cord. Therefore, the aim of this study was to explore and describe in detail the MR imaging features found in the spinal cord and nerve roots of infants with congenital Zika syndrome with or without arthrogryposis.     

Low-Power Inversion Recovery MRI Preserves Brain Tissue Contrast for Patients with Parkinson Disease with Deep Brain Stimulators

BACKGROUND AND PURPOSE:Fast spin-echo short τ inversion recovery sequences have been very useful for MR imaging–guided deep brain stimulation procedures in Parkinson disease. However, high-quality fast spin-echo imaging deposits significant heat, exceeding FDA-approved limits when patients already have undergone deep brain stimulation and need a second one or a routine brain MR imaging for neurologic indications. We have developed a STIR sequence with an ultra-low specific absorption rate that meets hardware limitations and produces adequate tissue contrast in cortical and subcortical brain tissues for deep brain stimulation recipients.MATERIALS AND METHODS:Thirteen patients with medically refractory Parkinson disease who qualified for deep brain stimulation were imaged at 1.5T with a fast spin-echo short τ inversion recovery sequence modified to meet conditional MR imaging hardware and specific absorption rate restrictions. Tissue contrast-to-noise ratios and implant localization were objectively and subjectively compared by 2 neuroradiologists, and image quality for surgical planning was assessed by a neurosurgeon for high and low specific absorption rate images.RESULTS:The mean contrast-to-noise ratio for cerebral tissues without including the contrast-to-noise ratio for ventricular fluid was 35 and 31 for high and low specific absorption rate images. Subjective ratings for low specific absorption rate tissue contrast in 77% of patients were identical to (and in a few cases higher than) those of high specific absorption rate contrast, while the neurosurgical coordinates for fusing the stereotactic atlas with low specific absorption rate MR imaging were equivalent to those of the high specific absorption rate for 69% of patients.CONCLUSIONS:Patients with Parkinson disease who have already had a deep brain stimulation face a risk of neural injury if routine, high specific absorption rate MR imaging is performed. Our modified fast spin-echo short τ inversion recovery sequence conforms to very conservative radiofrequency safety limits, while it maintains high tissue contrast for presurgical planning, postsurgical assessment, and radiologic evaluations with greater confidence for radiofrequency safety.

The diagnostic quality and radiofrequency (RF) safety of MR imaging for visualizing the subthalamic nucleus (STN) and globus pallidus are not simultaneously achievable, though both are crucial for surgical accuracy and treatment efficacy of deep brain stimulation (DBS) procedures^1–3 in patients with drug-refractory Parkinson disease (PD). Kitajima et al³ observed significantly better, though not perfect, mapping of the STN by using inversion recovery (fast spin-echo short τ inversion recovery [FSTIR]) sequences. Ben-Haim et al⁴ reported improved STN targeting by combining FSTIR and contrast-enhanced spoiled gradient-recalled-echo acquisitions. Although not currently approved for DBS recipients, higher fields show clear delineation of the STN at 7T.^5–7The deposited RF power (specific absorption rate [SAR]) increases with field strength; and the effective sequences, including FSTIR or T2, pose significant RF heating risk,⁸ which has been a potential deterrent for MR imaging of DBS recipients.⁹ Although experiences of incident-free routine high-SAR brain MR imaging in large groups of DBS patients have been reported^2,10 and sentinel events, including serious brain injury or death, are very few,¹¹ some researchers observed¹² a greater incidence of neurologic deficits and tissue edema surrounding electrodes in DBS recipients after routine MR imaging that perhaps were not caused by the surgical procedure itself. Note that local SAR near the contact points at the DBS electrode base is unknown, and because DBS belongs to a class of critical-length implants, the SAR can be an order of magnitude higher.¹³ Concerns about local heating and the variability of SAR among MR imaging machines^14,15 have led to strict MR imaging conditional labeling.^16,17 This has limited the choice of MR sequences and hardware with consequent loss of image quality. Using low-refocusing flip angle^18,19 high-quality brain imaging on healthy controls at a low SAR has been possible,²⁰ though this approach cannot be directly applied to DBS recipients due to hardware restrictions.^16,17 High-quality FSE imaging seems to require use of high RF power and thus is restricted to planning the first DBS only. A repeat of the high SAR sequence for high-quality FSE is not recommended for implanting a second DBS or for revising prior ones due to excessive local SAR. We propose to minimize such risks, though without completely eliminating them, by an ultra-low SAR high-resolution sequence and to test its utility for diagnostic and presurgical use.The primary cause of heating at the implant tips with FSE sequences is due to the fast application of multiple high flip angle refocusing RF pulses. We used a high-SAR FSTIR sequence (1.5 W/kg) on DBS surgical candidates (with no electrodes) for presurgical planning for the first DBS and compared the tissue contrast by performing an ultra-low SAR MR imaging (≤0.1 W/kg or 15 times lower) on the same patients for planning additional DBS or for revising the prior ones. The resulting images were assessed both subjectively and objectively for cerebral tissue contrast.     

Prevalence of Radiologically Isolated Syndrome and White Matter Signal Abnormalities in Healthy Relatives of Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE:The exact prevalence of WM signal abnormalities in healthy relatives of MS patients and their impact on disease development has not been fully elucidated. The purpose of this study was to compare WM signal abnormality characteristics and the prevalence of radiologically isolated syndrome in healthy control subjects selected randomly from the population with the healthy relatives of patients with MS.MATERIALS AND METHODS:Healthy control subjects (n = 150) underwent physical and 3T MR imaging examinations. Healthy control subjects were classified as non-familial healthy control subjects (n = 82) if they had no family history of MS or as healthy relatives of patients with MS (n = 68) if they had ≥1 relative affected with MS. The presence of radiologically isolated syndrome was evaluated according to the Okuda criteria; dissemination in space on MR imaging and fulfillment of radiologically isolated syndrome criteria were also evaluated according to Swanton criteria.RESULTS:There was a significantly higher total volume of WM signal abnormality in the healthy relatives of patients with MS compared with the non-familial healthy control subjects (P = .024 for signal abnormality ≥3 mm in size and P = .025 for all sizes). Periventricular localization and the number of lesions in all groups (P = .034 and P = .043) were significantly higher in the healthy relatives of patients with MS; 8.8% of the healthy relatives of patients with MS and 4.9% of non-familial healthy control subjects showed ≥9 WM signal abnormalities; 2.9% of subjects in the healthy relatives of patients with MS group and 2.4% of non-familial healthy control subjects fulfilled radiologically isolated syndrome according to the Okuda criteria, whereas 10.3% and 3.7% of subjects fulfilled radiologically isolated syndrome according to the Swanton criteria. In the healthy relatives of patients with MS, smoking was associated with the presence of WM signal abnormalities, whereas obesity was related to the presence of ≥9 WM signal abnormalities and to fulfillment of radiologically isolated syndrome according to the Swanton criteria.CONCLUSIONS:The frequency of WM signal abnormalities and radiologically isolated syndrome is higher in the healthy relatives of patients with multiple sclerosis patients compared with non-familial healthy control subjects.

Multiple sclerosis is an inflammatory autoimmune demyelinating disorder of the CNS.¹ Although MS is predominantly a sporadic disease, a genetic predisposition to developing familial MS is well accepted.² Although the exact definition of familial MS is not yet established, familial patients with MS are considered to be those with ≥1 first-degree relative affected with MS,² although some authors use a definition that is based on the presence of 2 first-degree relatives.³ In a recent meta-analysis, the risk of development of MS was 18.2% for monozygotic twins of patients with MS, 4.6% for dizygotic twins, and 2.7% for siblings.⁴ The risk of development of MS in a first-degree relative of the affected patient is 30- to 50-fold higher than in the general population,⁵ whereas second- and third-degree relatives also showed an increased risk for development of MS.⁶Whether familial or non-familial MS are different forms of the disease is not fully elucidated yet.⁷ Differences in disease progression in familial MS were observed in several studies demonstrating earlier age of onset and increased probability of a progressive clinical course.⁸ However, other studies did not show clinical differences among familial and non-familial healthy control subject (non-fMS) forms.^2,9 Nevertheless, MR imaging studies by use of nonconventional techniques showed MR imaging differences between familial and non-familial MS.^10–12In 2009, Okuda et al¹³ introduced the term “radiologically isolated syndrome” (RIS) to describe subjects who show incidental brain MR imaging WM lesions suggestive of MS and who fulfill Barkhof criteria for dissemination in space (DIS)¹⁴ but have no signs or symptoms of the disease. Overall, the prevalence of RIS is, according to postmortem studies, in a range of 0.06–0.7%, with an age range of 16–70.^13,15 However, the McDonald 2010 criteria for DIS¹⁶ substituted Barkhof criteria¹⁴ with the Swanton criteria for DIS.¹⁷ Swanton DIS criteria require the presence of ≥1 WM lesion in ≥2 of the brain regions (juxtracortical, periventricular, or infratentorial) or in the spinal cord.¹⁷ The value of the Swanton criteria for DIS¹⁷ was not evaluated with respect to the diagnosis of RIS.Previous MR imaging studies showed that asymptomatic relatives of patients with MS display significant magnetization transfer ratio changes in CNS WM signal abnormality, indicative of MS pathology,^3,18 though some other studies showed no differences in the magnetization transfer ratio of WM in the siblings of patients with MS.¹⁹ Studies with the use of conventional brain MR imaging showed WM signal abnormalities consistent with MS in the healthy relatives of patients with MS,^20–22 with 4% of non-familial healthy control subjects (non-fHC) and 10% of healthy control subjects with familial MS (HC) fulfilling Barkhof criteria¹⁴ for DIS.²⁰ However, these studies had several limitations including the number of enrolled subjects, strength of the MR imaging field, and use of more conservative criteria for RIS.¹³ As a result, the exact prevalence of RIS and the WM signal abnormalities in asymptomatic MS relatives is not yet fully defined.The aim of this pilot study was to compare WM signal abnormality characteristics in a large cohort of non-fHCs and healthy relatives of patients with MS by use of 3T MR imaging. We also determined the prevalence of RIS in HC groups, according to both the Barkhof¹⁴ and Swanton¹⁷ MR imaging criteria for DIS and investigated association between the presence of vascular risk factors and RIS.     

Fellows' Journal Club: Brain MRI Findings in Neurologically Asymptomatic Patients with Infective Endocarditis

BACKGROUND AND PURPOSE:Neurologic complications in infective endocarditis are frequent and affect patient prognosis negatively. Additionally, detection of asymptomatic lesions by MR imaging could help early management of this condition. The objective of our study was to describe MR imaging characteristics of cerebral lesions in a neurologically asymptomatic population with infective endocarditis.MATERIALS AND METHODS:One hundred nine patients at the acute phase of a definite or possible infective endocarditis according to the Duke modified criteria and without neurologic manifestations according to the NIHSS were prospectively included. Each patient underwent cerebral MR imaging and MRA within 7 days of admission.RESULTS:MR imaging showed abnormalities in 78 patients (71.5%). Acute ischemic lesions (40 patients, 37%) and cerebral microbleeds (62 patients, 57%) were the most frequent lesions. Eight patients had an acute SAH, 3 patients had brain microabscesses, 3 had a small cortical hemorrhage, and 3 had a mycotic aneurysm. Acute ischemic lesions mostly appeared as multiple small infarcts disseminated in watershed territories (25/40, 62.5%) and as lesions of different ages (21/40, 52.5%). Cerebral microbleeds were preferentially distributed in cortical areas (362/539 cerebral microbleeds, 67%). No significant correlation was found among lesions, in particular between acute ischemia and cerebral microbleeds.CONCLUSIONS:Occult cerebral lesions, in particular cerebral microbleeds and acute ischemic lesions, are frequent in infective endocarditis. The MR imaging pattern of acute small infarcts of different ages predominating in watershed territories and cortical cerebral microbleeds may represent a surrogate imaging marker of infective endocarditis.

Infective endocarditis is associated with symptomatic neurologic complications in 20%–40% of cases.^1–4 Among symptomatic complications, ischemic stroke is the most common manifestation, whereas hemorrhagic stroke, brain abscess, cerebral hemorrhage or SAH, and mycotic aneurysms are less frequent.² Symptomatic cerebral complications are one of the main prognostic factors in infective endocarditis (IE)^5–8 because they are significantly associated with a 3-month mortality rate.^2,3,9,10 Symptomatic neurologic complications are difficult to predict and prevent because they mostly occur in the early phase of IE and have been reported as the presenting symptom of the disease in up to 47% of cases.²Asymptomatic cerebral lesions revealed by systematic cerebral CT and/or MR imaging have been recently reported, but their impact on patient care and prognosis has not been completely assessed.^8,11–13 Our group showed that detection of cerebral asymptomatic lesions influenced diagnostic decisions in cases of suspected IE.^14,15The purposes of the present study were to extensively describe MR imaging characteristics of cerebral lesions in a neurologically asymptomatic population at the acute phase of IE, to prospectively report their respective frequencies, and to assess correlations between different MR imaging features.     

Early-Stage Glioblastomas: MR Imaging–Based Classification and Imaging Evidence of Progressive Growth

BACKGROUND AND PURPOSE:The serial imaging changes describing the growth of glioblastomas from small to large tumors are seldom reported. Our aim was to classify the imaging patterns of early-stage glioblastomas and to define the order of appearance of different imaging patterns that occur during the growth of small glioblastomas.MATERIALS AND METHODS:Medical records and preoperative MR imaging studies of patients diagnosed with glioblastoma between 2006 and 2013 were reviewed. Patients were included if their MR imaging studies showed early-stage glioblastomas, defined as small MR imaging lesions detected early in the course of the disease, demonstrating abnormal signal intensity but the absence of classic imaging findings of glioblastoma. Each lesion was reviewed by 2 neuroradiologists independently for location, signal intensity, involvement of GM and/or WM, and contrast-enhancement pattern on MR imaging.RESULTS:Twenty-six patients with 31 preoperative MR imaging studies met the inclusion criteria. Early-stage glioblastomas were classified into 3 types and were all hyperintense on FLAIR/T2-weighted images. Type I lesions predominantly involved cortical GM (n = 3). Type II (n = 12) and III (n = 16) lesions involved both cortical GM and subcortical WM. Focal contrast enhancement was present only in type III lesions at the gray-white junction. Interobserver agreement was excellent (κ = 0.95; P < .001) for lesion-type classification. Transformations of lesions from type I to type II and type II to type III were observed on follow-up MR imaging studies. The early-stage glioblastomas of 16 patients were pathologically confirmed after imaging progression to classic glioblastoma.CONCLUSIONS:Cortical lesions may be the earliest MR imaging–detectable abnormality in some human glioblastomas. These cortical tumors may progress to involve WM.

Glioblastoma (GB) is the most common primary malignant brain tumor. It typically appears as a large mass with necrosis, prominent edema, mass effect, and strong heterogeneous contrast enhancement when diagnosed. MR imaging, a noninvasive diagnostic tool with excellent tissue contrast, has the potential to detect small GBs. However, it is uncommon to detect small GBs clinically, probably due to nonspecific or absent symptoms. The serial imaging changes depicting the growth of GBs from small to large tumors are seldom reported.Some reports described small MR imaging lesions that subsequently progressed to GBs.^1–11 These are often described as ill-defined, FLAIR or T2-weighted hyperintensities without discernable mass effect that typically involve both the cortex and subcortical WM, but occasionally appear as only cortical lesions.^2,4,8 Contrast enhancement is not a consistent feature and tends to be focal and nodular when present.^6–8 The commonly affected brain areas include frontal (n = 4),^2,3,6,8 parietal (n = 2),^7,10 occipital (n = 1),¹¹ temporal (n = 5),^2,3,6,7,11 hippocampal (n = 3),^1,2,9 and insular (n = 1)⁹ regions. Because these MR imaging lesions were detected early in the course of the disease, they were frequently referred to as early-stage GBs.^3,5–8,11We have noticed different imaging patterns in early-stage GBs. An imaging classification for early-stage GB, however, is not available because most previous studies included only a few such cases. It is important for radiologists to be familiar with early imaging findings and growth patterns of GBs because familiarity may help diagnose small tumors that are symptomatic or incidentally found. Early diagnosis of GB may lead to a higher extent of tumor resection, which has been demonstrated to correlate with patient survival.¹² In this study, we aimed to classify the imaging patterns of early-stage GBs and to the define the order of appearance of different imaging patterns that occur during the growth of these tumors.