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.     

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.     

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.     

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.     

Transition into Driven Equilibrium of the Balanced Steady-State Free Precession as an Ultrafast Multisection T2-Weighted Imaging of the Brain

BACKGROUND AND PURPOSE:Current T2-weighted imaging takes >3 minutes to perform, for which the ultrafast transition into driven equilibrium (TIDE) technique may be potentially helpful. This study qualitatively and quantitatively evaluates the imaging of transition into driven equilibrium of the balanced steady-state free precession (TIDE) compared with TSE and turbo gradient spin-echo on T2-weighted MR images.MATERIALS AND METHODS:Thirty healthy volunteers were examined with T2-weighted images by using TIDE, TSE, and turbo gradient spin-echo sequences. Imaging was evaluated qualitatively by 2 independent observers on the basis of a 4-point rating scale regarding contrast characteristics and artifacts behavior. Image SNR and contrast-to-noise ratio were quantitatively assessed.RESULTS:TIDE provided T2-weighted contrast similar to that in TSE and turbo gradient spin-echo with only one-eighth of the scan time. TIDE showed gray-white matter differentiation and iron-load sensitivity inferior that of TSE and turbo gradient spin-echo, but with improved motion artifacts reduction on qualitative scores. Nonmotion ghosting artifacts were uniquely found in TIDE images. The overall SNRs of TSE were 1.9–2.0 times those of turbo gradient spin-echo and 1.7–2.2 times of those of TIDE for brain tissue (P < .0001). TIDE had a higher contrast-to-noise ratio than TSE (P = .169) and turbo gradient spin-echo (P < .0001) regarding non-iron-containing gray matter versus white matter. TIDE had a lower contrast-to-noise ratio than turbo gradient spin-echo and TSE (P < .0001) between iron-containing gray matter and white matter.CONCLUSIONS:TIDE provides T2-weighted images with reduced scan times and reduced motion artifacts compared with TSE and turbo gradient spin-echo with the trade-off of reduced SNR and poorer gray-white matter differentiation.

T2-weighted MR images are commonly used to depict gross pathologic changes of the brain, including tumor, infarction, ischemia, white matter demyelination, inflammation, edema, and so forth.^1–4 The turbo spin-echo sequence is a method currently used for routine T2WI examination in the brain and in other extracranial regions.^5,6 In daily practice, it often takes >3 minutes to obtain 1 set of 2D TSE T2WIs on a certain plane.^5–7 Accordingly, it might take as long as 10 minutes to obtain T2WI on 3 orthogonal planes by using TSE. Although 3D imaging techniques have been developed to acquire T2WI, they still take as long as 6–8 minutes of acquisition time,^8–10 which makes them prone to motion artifacts and hampers their clinical application in daily practice.There is an increasing need for a fast imaging technique to acquire T2WI of the brain in patients with motion during MR imaging. In 2000, Chung et al¹¹ demonstrated the advantage of a fast imaging with steady-state free precession to freeze the fetal motion during MR imaging. However, true fast imaging with steady-state precession carries a contrast known as T2/T1 rather than T2-weighted. The transition into driven equilibrium is a variant of the balanced steady-state free precession technique, inheriting characteristics of balanced steady-state free precession like high SNR efficiency and flow compensation. Different from the T2/T1 contrast of conventional balanced steady-state free precession,^11,12 pure T2 contrast or T2-weighted contrast with fat suppression can be rendered by transition into driven equilibrium (TIDE) theoretically, depending on the sampling strategy of the contrast-determining central k-space.^13–17 The typical scan time of TIDE for a single section is approximately 1 second, which is desirable, especially when 3-plane multisection T2WIs are considered for clinical practice, such as for rapid screening or diagnosis. Before applying them to daily practice, however, the imaging quality and characteristics of TIDE need to be evaluated.We assume that TIDE could also provide T2-weighted imaging contrast similar to that in other pulse sequences, including TSE and turbo gradient spin-echo (TGSE). In this study, we aimed to qualitatively and quantitatively evaluate TIDE compared with TSE and TGSE in T2-weighted brain MR images.     

Differentiation between Treatment-Induced Necrosis and Recurrent Tumors in Patients with Metastatic Brain Tumors: Comparison among 11C-Methionine-PET,FDG-PET,MR Permeability Imaging,and MRI-ADC—Preliminary Results

BACKGROUND AND PURPOSE:In patients with metastatic brain tumors after gamma knife radiosurgery, the superiority of PET using ¹¹C-methionine for differentiating radiation necrosis and recurrent tumors has been accepted. To evaluate the feasibility of MR permeability imaging, it was compared with PET using ¹¹C-methionine, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumors.MATERIALS AND METHODS:The study analyzed 18 lesions from 15 patients with metastatic brain tumors who underwent gamma knife radiosurgery. Ten lesions were identified as recurrent tumors by an operation. In MR permeability imaging, the transfer constant between intra- and extravascular extracellular spaces (/minute), extravascular extracellular space, the transfer constant from the extravascular extracellular space to plasma (/minute), the initial area under the signal intensity–time curve, contrast-enhancement ratio, bolus arrival time (seconds), maximum slope of increase (millimole/second), and fractional plasma volume were calculated. ADC was also acquired. On both PET using ¹¹C-methionine and FDG-PET, the ratio of the maximum standard uptake value of the lesion divided by the maximum standard uptake value of the symmetric site in the contralateral cerebral hemisphere was measured (¹¹C-methionine ratio and FDG ratio, respectively). The receiver operating characteristic curve was used for analysis.RESULTS:The area under the receiver operating characteristic curve for differentiating radiation necrosis from recurrent tumors was the best for the ¹¹C-methionine ratio (0.90) followed by the contrast-enhancement ratio (0.81), maximum slope of increase (millimole/second) (0.80), the initial area under the signal intensity–time curve (0.78), fractional plasma volume (0.76), bolus arrival time (seconds) (0.76), the transfer constant between intra- and extravascular extracellular spaces (/minute) (0.74), extravascular extracellular space (0.68), minimum ADC (0.60), the transfer constant from the extravascular extracellular space to plasma (/minute) (0.55), and the FDG-ratio (0.53). A significant difference in the ¹¹C-methionine ratio (P < .01), contrast-enhancement ratio (P < .01), maximum slope of increase (millimole/second) (P < .05), and the initial area under the signal intensity–time curve (P < .05) was evident between radiation necrosis and recurrent tumor.CONCLUSIONS:The present study suggests that PET using ¹¹C-methionine may be superior to MR permeability imaging, ADC, and FDG-PET for differentiating radiation necrosis from recurrent tumors after gamma knife radiosurgery for metastatic brain tumors.

Stereotactic radiosurgery such as gamma knife radiosurgery (GK) and CyberKnife (Accuray, Sunnyvale, California) is an effective method for treating intracranial neoplasms.^1,2 For metastatic tumors of the brain, stereotactic radiosurgery has generally been the main tool used in therapeutic regimens.^3,4 Although stereotactic radiosurgery is an effective treatment method, it has a risk of radiation necrosis. Radiation necrosis after stereotactic radiosurgery for metastatic tumors of the brain is more common than previously reported.^5,6 It generally occurs 3–12 months after therapy⁷ and often resembles recurrent tumors on conventional imaging techniques, such as MR imaging,^8–11 CT,¹² and SPECT.¹³ Differentiating radiation necrosis and recurrent tumor is extremely important because of the different treatment implications. Histologic examination from a biopsy or resection may aid in differentiating these 2 events. However, a noninvasive method is needed for diagnosing whether a contrast-enhanced lesion with surrounding edema on conventional MR imaging is radiation necrosis or a recurrent tumor.Advanced MR imaging techniques including MR spectroscopy,¹⁴ DWI,¹⁵ and DTI¹⁶ have been used for differentiation of radiation necrosis and recurrent tumors. The CTP technique has also been reported as promising in this field.¹⁷ CTP has the advantage of using widely available CT scanners, though x-ray exposure and administration of ionizing contrast material limit the clinical use. In radionuclide studies, SPECT with ²⁰¹TI-chloride,¹⁸ technetium Tc99m-sestamibi,^{19 123}I-alfa-methyl-L-tyrosine,²⁰O-(2-[¹⁸F]-fluoroethyl)-L-tyrosine (FET-PET),^21,22 6-[¹⁸F]-fluoro-L-dopa (FDOPA),²³ and FDG-PET^24–26 have been reported to differentiate between radiation necrosis and recurrent tumors. Compared with those studies, the superiority of PET with ¹¹C-methionine (MET) for differentiating radiation necrosis and recurrent tumors has been accepted because of the high sensitivity and specificity.^27–31 However, MET-PET is not widely available. Dynamic contrast-enhanced MR imaging with a contrast agent has been used to characterize brain tumors^32,33 and stroke.³⁴MR permeability imaging with dynamic contrast-enhanced–MR imaging based on the Tofts model³⁵ has recently been developed and used for evaluating cerebrovascular diseases,³⁶ brain tumors,^37–39 nasopharyngeal carcinomas,^40,41 rectal carcinomas,⁴² and prostate carcinomas.⁴³ The endothelial permeability of vessels in brain tumors can be quantitatively acquired with MR permeability imaging. The vascular microenvironment in tumors can be measured by parameters such as influx transfer constant, reverse transfer constant, and the extravascular extracellular space.⁴⁴ These parameters may reflect tissue characteristics including vascular density, a damaged blood-brain barrier, vascularity, and neoangiogenesis.⁴⁴ If the feasibility of MR permeability imaging for differentiating radiation necrosis and recurrent tumors could be demonstrated, this technique may contribute to the management of patients after stereotactic radiosurgery and conventional radiation therapy because MR permeability imaging is widely available. To evaluate the feasibility of MR permeability imaging in the present study, we compared it with MET-PET, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumor after GK in patients with metastatic brain tumors.     

Brain MRI Measurements at a Term-Equivalent Age and Their Relationship to Neurodevelopmental Outcomes

BACKGROUND AND PURPOSE:An increased prevalence of disabilities is being observed as more preterm infants survive. This study was conducted to evaluate correlations between brain MR imaging measurements taken at a term-equivalent age and neurodevelopmental outcome at 2 years'' corrected age among very low–birth-weight infants.MATERIALS AND METHODS:Of the various brain MR imaging measurements obtained at term-equivalent ages, reproducible measurements of the transcerebellar diameter and anteroposterior length of the corpus callosum on sagittal images were compared with neurodevelopmental outcomes evaluated by the Bayley Scales of Infant Development (II) at 2 years'' corrected age (mean ± standard deviation, 16.1 ± 6.4 months of age).RESULTS:Ninety infants were enrolled. The mean gestational age at birth was 27 weeks and the mean birth weight was 805.5 g. A short corpus callosal length was associated with a Mental Developmental Index <70 (P = .047) and high-risk or diagnosed cerebral palsy (P = .049). A small transcerebellar diameter was associated with a Psychomotor Developmental Index <70 (P = .003), Mental Developmental Index <70 (P = .004), and major neurologic disability (P = .006).CONCLUSIONS:A small transcerebellar diameter and short corpus callosal length on brain MR imaging at a term-equivalent age are related to adverse neurodevelopmental outcomes at a corrected age of 2 years and could be a useful adjunctive tool for counseling parents about future developmental outcomes.

The survival rate of preterm infants has increased with the advances in neonatal care in recent decades. However, a higher prevalence of disabilities has also been observed in survivors of preterm birth at infancy and in childhood.^1,2 Factors such as intraventricular hemorrhage,³ hypoxia, prematurity,^3–5 and neonatal care^3,6 have been reported to affect the developing brain; the mechanism of injury during the development of the cerebellum and corpus callosum in surviving premature infants may be caused by primary destruction or underdevelopment⁷ and axonal injury,⁸ respectively. These factors in turn result in an altered brain volume or structure that can be seen as a reduced cerebral and/or cerebellar volume,^3,9,10 subarachnoid space widening,^3,6,11 corpus callosum thinning,^12–14 and posthemorrhagic ventricular dilation on brain MR imaging.¹⁵ These findings have led to reports of various measurements of MR imaging as potential predictors of neurologic outcomes at infancy or in childhood.^10,14,16,17We conducted a study in a single neonatal intensive care unit (NICU) to evaluate correlations between brain MR imaging measurements taken at term-equivalent age and the neurodevelopmental outcomes at 2 years'' corrected age.     

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.     

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.     

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.     

Direct Visualization of Anatomic Subfields within the Superior Aspect of the Human Lateral Thalamus by MRI at 7T

BACKGROUND AND PURPOSE:The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T.MATERIALS AND METHODS:The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.5²-mm² in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution.RESULTS:Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus.CONCLUSIONS:Inversion recovery–prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future.

MR imaging, due to its excellent soft-tissue-contrast capabilities, has become the most important imaging technique for the living brain. Nevertheless, the thalamus, characterized by its rich structural variety,^1–3 appears virtually isointense in routine high-resolution MR images. The lack of visible anatomic detail within the thalamus affects presurgical planning of deep brain stimulation (DBS) procedures. Considering that thalamic morphology can show significant interindividual variability,³ direct visualization of intrathalamic anatomy is necessary for a more precise patient-specific planning of brain electrode positions.Besides the small size of some thalamic nuclei, the main reason for the lack of contrast is the similarity of MR imaging–relevant tissue parameters such as relaxation times and/or proton densities of adjacent thalamic structures. However, as long as differences in contrast-relevant tissue properties exist, their delineation by an appropriate MR imaging technique is mainly a question of SNR. Several years ago, the wide availability of 3T MR imaging scanners triggered a series of studies aiming to visualize internal substructures of the thalamus,^4–11 extending the research done at 1.5T.^12–16 Although noticeable progress was made, the visualization of thalamic nuclei with 3T MR imaging for DBS surgery is not a clinical routine to date. It seemed reasonable to assume that the SNR boost offered by MR imaging at 7T could further improve the visualization of thalamic nuclei. Indeed, the first encouraging results have been reported by using SWI, quantitative susceptibility mapping, and MPRAGE imaging.^17–19 This feasibility study aims to investigate the usefulness of inversion recovery turbo-spin-echo (IR-TSE) MR imaging at 7T in revealing anatomic detail within the thalamus. This task comprises both the optimization of the MR imaging acquisition and the assignment of visualized structures to thalamic anatomy.     

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.     

Arterial Spin-Labeled Perfusion of Pediatric Brain Tumors

BACKGROUND AND PURPOSE:Pediatric brain tumors have diverse pathologic features, which poses diagnostic challenges. Although perfusion evaluation of adult tumors is well established, hemodynamic properties are not well characterized in children. Our goal was to apply arterial spin-labeling perfusion for various pathologic types of pediatric brain tumors and evaluate the role of arterial spin-labeling in the prediction of tumor grade.MATERIALS AND METHODS:Arterial spin-labeling perfusion of 54 children (mean age, 7.5 years; 33 boys and 21 girls) with treatment-naive brain tumors was retrospectively evaluated. The 3D pseudocontinuous spin-echo arterial spin-labeling technique was acquired at 3T MR imaging. Maximal relative tumor blood flow was obtained by use of the ROI method and was compared with tumor histologic features and grade.RESULTS:Tumors consisted of astrocytic (20), embryonal (11), ependymal (3), mixed neuronal-glial (8), choroid plexus (5), craniopharyngioma (4), and other pathologic types (3). The maximal relative tumor blood flow of high-grade tumors (grades III and IV) was significantly higher than that of low-grade tumors (grades I and II) (P < .001). There was a wider relative tumor blood flow range among high-grade tumors (2.14 ± 1.78) compared with low-grade tumors (0.60 ± 0.29) (P < .001). Across the cohort, relative tumor blood flow did not distinguish individual histology; however, among posterior fossa tumors, relative tumor blood flow was significantly higher for medulloblastoma compared with pilocytic astrocytoma (P = .014).CONCLUSIONS:Characteristic arterial spin-labeling perfusion patterns were seen among diverse pathologic types of brain tumors in children. Arterial spin-labeling perfusion can be used to distinguish high-grade and low-grade tumors.

Brain tumors are the most common solid tumors of childhood and are a leading cause of cancer deaths in children.¹ Unlike in adults, these tumors predominate in the posterior fossa and have more heterogeneous pathologic features, including embryonal and mixed neuronal-glial types.² Because of their diverse histologic presentation and biologic behavior, evaluation and treatment of pediatric brain tumors remain complex.MR imaging is important in tumor diagnosis, surgical guidance, and therapeutic monitoring of brain tumors. Various PWI methods have shown clinical usefulness in adult glioma, including the use of relative maximal CBV and relative CBF from DSC-PWI to predict tumor grade and behavior.^3–10 Despite abundant literature on adult brain tumors, few perfusion reports exist for pediatric brain tumors,^11–14 potentially because of technical challenges. For example, the most widely available T2*-weighted DSC imaging often requires constant, high-flow contrast injection by power injectors, double-dosing, and large-bore intravenous access, which pose challenges in young children and infants.Recent studies have shown that arterial spin-labeling (ASL) may be a reliable alternative to DSC-PWI in the evaluation of tumor perfusion^15–20 and can predict adult glioma grade.¹⁶ ASL has distinct advantages in children because of lack of contrast requirement, high SNR, labeling efficiency, and the potential for CBF quantification. Also, ASL can be repeated in cases of failed sedation or patient motion, a frequent problem in children with brain tumors. Although ASL has become increasingly available clinically, no ASL data exist on pediatric brain tumors. Our goal was to apply ASL perfusion for diverse pathologic types of pediatric brain tumors and evaluate the use of ASL perfusion for the prediction of tumor grade in children.     

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.     

Brain Metabolic Abnormalities Associated with Developmental Venous Anomalies

BACKGROUND AND PURPOSE:Developmental venous anomalies are the most common intracranial vascular malformation and are typically regarded as inconsequential, especially when small. While there are data regarding the prevalence of MR imaging findings associated with developmental venous anomalies, FDG-PET findings have not been well-characterized.MATERIALS AND METHODS:Clinical information systems were used to retrospectively identify patients with developmental venous anomalies depicted on MR imaging examinations who had also undergone FDG-PET. Both the MR imaging and FDG-PET scans were analyzed to characterize the developmental venous anomalies and associated findings on the structural and functional scans. Qualitative and quantitative assessments were performed, including evaluation of the size of the developmental venous anomaly, associated MR imaging findings, and characterization of the FDG uptake in the region of the developmental venous anomaly.RESULTS:Twenty-five developmental venous anomalies in 22 patients were identified that had been characterized with both MR imaging and FDG-PET, of which 76% (19/25) were associated with significant metabolic abnormality in the adjacent brain parenchyma, most commonly hypometabolism. Patients with moderate and severe hypometabolism were significantly older (moderate: mean age, 65 ± 7.4 years, P = .001; severe: mean age, 61 ± 8.9 years, P = .008) than patients with developmental venous aberrancies that did not have abnormal metabolic activity (none: mean age, 29 ± 14 years).CONCLUSIONS:Most (more than three-quarters) developmental venous anomalies in our series of 25 cases were associated with metabolic abnormality in the adjacent brain parenchyma, often in the absence of any other structural abnormality. Consequently, we suggest that developmental venous anomalies may be better regarded as developmental venous aberrancies.

Adevelopmental venous anomaly (DVA) is a transparenchymal vein of greater than usual size into which coalesces a network of smaller veins, a configuration described as a caput medusa. DVAs may drain into either the superficial or deep venous systems and may occur in the cerebrum, cerebellum, brain stem, and spinal cord. DVAs are the most common intracranial vascular malformation, with a reported incidence of 2.6%.^1,2 The mechanism of DVA formation is still controversial. The term “developmental venous anomaly” was first coined by Lasjaunias et al³ to emphasize their belief that these are embryologic variants of venous drainage rather than true vascular anomalies.Brain parenchymal lesions have been widely reported in association with DVAs, with abnormalities apparent on angiography,⁴ CT⁵ and MR structural imaging,^6–8 and functional imaging methods such as perfusion and diffusion-weighted imaging.^9–12 Several case reports further exemplify how DVAs can be associated with clinical pathologies such as hemorrhagic transformation, ischemic complications, and epileptogenic foci.^13–16 Recent studies also indicate the possible role of DVAs in the formation of cavernous malformations.⁹ These findings suggest that the clinical significance of abnormal brain anatomy and activity near a DVA is uncertain and has yet to be accurately evaluated. Furthermore, our clinical experience has revealed metabolic abnormality associated with DVAs, as determined by FDG-PET. These findings led us to the hypothesis that the metabolic activity in brain parenchyma in the region of a DVA is abnormal. In this study, we sought to better understand metabolic activity in the region of DVAs as assessed by FDG-PET.     

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.     

Volume of Structures in the Fetal Brain Measured with a New Semiautomated Method

BACKGROUND AND PURPOSE:Measuring the volume of fetal brain structures is challenging due to fetal motion, low resolution, and artifacts caused by maternal tissue. Our aim was to introduce a new, simple, Matlab-based semiautomated method to measure the volume of structures in the fetal brain and present normal volumetric curves of the structures measured.MATERIALS AND METHODS:The volume of the supratentorial brain, left and right hemispheres, cerebellum, and left and right eyeballs was measured retrospectively by the new semiautomated method in MR imaging examinations of 94 healthy fetuses. Four volume ratios were calculated. Interobserver agreement was calculated with the intraclass correlation coefficient, and a Bland-Altman plot was drawn for comparison of manual and semiautomated method measurements of the supratentorial brain.RESULTS:We present normal volumetric curves and normal percentile values of the structures measured according to gestational age and of the ratios between the cerebellum and the supratentorial brain volume and the total eyeball and the supratentorial brain volume. Interobserver agreement was good or excellent for all structures measured. The Bland-Altman plot between manual and semiautomated measurements showed a maximal relative difference of 7.84%.CONCLUSIONS:We present a technologically simple, reproducible method that can be applied prospectively and retrospectively on any MR imaging protocol, and we present normal volumetric curves measured. The method shows results like manual measurements while being less time-consuming and user-dependent. By applying this method on different cranial and extracranial structures, anatomic and pathologic, we believe that fetal volumetry can turn from a research tool into a practical clinical one.

In pediatric and adult populations, 3D volumetric measurement of brain structures is an important tool for the assessment of neurologic patients. Automatic volumetry of the brain is used to diagnose and evaluate different pathologies such as Alzheimer disease, essential tremor, multiple sclerosis, and epilepsy.^1–4 During the past decade, with the increasing use of MR imaging in prenatal evaluation, attempts to implement brain volumetric measurements on fetal MR imaging have been made. However, fetal MR imaging presents unique challenges for interpretation and measuring capabilities, such as fetal motion, low resolution, and artifacts due to maternal tissue. Some studies have tried to overcome these difficulties by measuring the volume manually.^5,6 This method is very time-consuming and interpreter-dependent. Other studies have presented newly developed automatic algorithms to correct the artifacts and align the images affected by fetal motion. However, these methods are costly, not widely applicable, and may require changes in the routine fetal MR imaging protocol.^2,7–11In this study, we introduce a new, Matlab-based (MathWorks, Natick, Massachusetts) semiautomated method for measuring the volume of structures in the fetal brain. We measured 6 structures with this method in a relatively large group and calculated 4 volume ratios. We validated this method by measuring a small control group manually and comparing the results with the measurements of the same group obtained with the new method and assessed its interobserver reliability.     

Fetal Brain Anomalies Associated with Ventriculomegaly or Asymmetry: An MRI-Based Study

BACKGROUND AND PURPOSE:Fetal lateral ventriculomegaly is a relatively common finding with much debate over its clinical significance. The purpose of this study was to examine the association between ventriculomegaly and asymmetry and concomitant CNS findings as seen in fetal brain MR imaging.MATERIALS AND METHODS:Fetal brain MR imaging performed for various indications, including ventriculomegaly, with or without additional ultrasound findings, was assessed for possible inclusion. Two hundred seventy-eight cases found to have at least 1 lateral ventricle with a width of ≥10 mm were included in the study. Ventriculomegaly was considered mild if the measurement was 10–11.9 mm; moderate if, 12–14.9 mm; and severe if, ≥15 mm. Asymmetry was defined as a difference of ≥2 mm between the 2 lateral ventricles. Fetal brain MR imaging findings were classified according to severity by predefined categories.RESULTS:The risk of CNS findings appears to be strongly related to the width of the ventricle (OR, 1.38; 95% CI, 1.08–1.76; P = .009). The prevalence of associated CNS abnormalities was significantly higher (P = .005) in symmetric ventriculomegaly compared with asymmetric ventriculomegaly (38.8% versus 24.2%, respectively, for all CNS abnormalities and 20% versus 7.1%, respectively, for major CNS abnormalities).CONCLUSIONS:In this study, we demonstrate that the rate of minor and major findings increased with each millimeter increase in ventricle width and that the presence of symmetric ventricles in mild and moderate ventriculomegaly was a prognostic indicator for CNS abnormalities.

Fetal lateral ventriculomegaly is a relatively common finding. Some have estimated the incidence of ventriculomegaly identified on sonography to be about 1%.¹ Fetal ventriculomegaly is defined as a dilation of the lateral ventricle atrium to a width of ≥10 mm.^2,3 A measurement of 10–12 mm is commonly referred to as mild ventriculomegaly, while measurements of 12–15 and >15 mm are defined as moderate and severe ventriculomegaly, respectively.⁴ Severe ventriculomegaly has been associated with poorer neurodevelopmental outcome compared with mild ventriculomegaly^5,6; however, it has been previously suggested that the neurodevelopmental outcome in cases of moderate ventriculomegaly is similar to that observed in mild ventriculomegaly.⁷Many studies have focused on the neurodevelopmental outcome of children who were diagnosed in utero with lateral ventriculomegaly.^6,8–16 One of the most important factors determining outcome is the presence and severity of additional CNS anomalies. Although most anomalies can be identified by using sonography, MR imaging was shown to be superior in identifying CNS anomalies. A recent study found that MR imaging could detect additional findings in 15.3% of the seemingly isolated ventriculomegaly/ventricle asymmetry cases.¹⁷ In this study, we aimed to establish the proportion of MR imaging–detected CNS anomalies associated with ventriculomegaly in correlation with the severity of ventriculomegaly and ventricle asymmetry. To prevent underestimation of associated anomalies, we did not exclude cases with CNS anomalies previously identified on sonography. To the best of our knowledge, this is the first large-scale MR imaging study that has examined the association between lateral ventricle width and asymmetry and CNS anomalies.     

Multimodal Imaging in Malignant Brain Tumors: Enhancing the Preoperative Risk Evaluation for Motor Deficits with a Combined Hybrid MRI-PET and Navigated Transcranial Magnetic Stimulation Approach

BACKGROUND AND PURPOSE:Motor deficits in patients with brain tumors are caused mainly by irreversible infiltration of the motor network or by indirect mass effects; these deficits are potentially reversible on tumor removal. Here we used a novel multimodal imaging approach consisting of structural, functional, and metabolic neuroimaging to better distinguish these underlying causes in a preoperative setting and determine the predictive value of this approach.MATERIALS AND METHODS:Thirty patients with malignant brain tumors involving the central region underwent a hybrid O-(2-[¹⁸F]fluoroethyl)-L-tyrosine–PET-MR imaging and motor mapping by neuronavigated transcranial magnetic stimulation. The functional maps served as localizers for DTI tractography of the corticospinal tract. The spatial relationship between functional tissue (motor cortex and corticospinal tract) and lesion volumes as depicted by structural and metabolic imaging was analyzed.RESULTS:Motor impairment was found in nearly all patients in whom the contrast-enhanced T1WI or PET lesion overlapped functional tissue. All patients who functionally deteriorated after the operation showed such overlap on presurgical maps, while the absence of overlap predicted a favorable motor outcome. PET was superior to contrast-enhanced T1WI for revealing a motor deficit before the operation. However, the best correlation with clinical impairment was found for T2WI lesion overlap with functional tissue maps, but the prognostic value for motor recovery was not significant.CONCLUSIONS:Overlapping contrast-enhanced T1WI or PET-positive signals with motor functional tissue were highly indicative of motor impairment and predictive for surgery-associated functional outcome. Such a multimodal diagnostic approach may contribute to the risk evaluation of operation-associated motor deficits in patients with brain tumors.

Multimodal imaging is a criterion standard in the diagnosis of brain tumors.¹ The combination of anatomic, functional, and metabolic imaging by MR imaging and PET helps differentiate tumor tissue from functionally relevant brain regions (eg, the primary motor cortex [M1]).² A frequently encountered phenomenon in patients presenting with tumors in the vicinity of motor regions is that some of them have motor impairment while others do not, and some deteriorate after the operation while others may even improve.^3–5 In some patients, motor deficits can be explained by direct infiltration of the tumor into the motor cortex or corticospinal tract (CST), while in other patients, compression effects resulting from the tumor mass and/or perifocal edema may cause motor symptoms.⁵ Differentiating causes is, however, highly relevant with respect to the reversibility of symptoms and planning of operations.^6–9In clinical practice, such preoperative diagnostics usually rely on analyses of structural MR imaging sequences such as T1- or T2-weighted scans without integrating individual information on functional anatomy. Direct cortical stimulation remains the criterion standard for motor function mapping but is limited to the intraoperative setting and, thus, not suitable for preoperative planning and risk evaluation. However, the repertoire of methods available in brain mapping has considerably advanced in the past decade and now allows elaborate analyses of structure-function relationships. For example, a useful tool for assessing the functional anatomy of the primary motor cortex in a noninvasive fashion is navigated transcranial magnetic stimulation (nTMS).^10–12 This technique has a reliability similar to that of fMRI mapping, however, with less demand for the cooperation of patients who may have reduced alertness, compliance, and functional impairment such as those with brain tumors.^13,14 Another technique that adds information to structure-function relationships is diffusion imaging, especially DTI.^9,15,16 For example, DTI-based tractography has been developed to visualize the subcortical fiber tracts in individual subjects; this is especially useful in conditions in which the functional anatomy can be heavily distorted such as in patients with brain tumors.^17,18 In addition, DTI can also be used to characterize the altered diffusion metrics within the tumor mass and the surrounding tissue, thereby allowing quantification of the integrity of fiber tracts.^19,20In summary, there are currently rather limited data on how to preoperatively evaluate patients with brain tumors for operation-associated risks related to motor impairment and recovery thereof.^7,12,21–23 Thus, the objective of our study was to use a multimodal imaging setup to delineate malignant brain tumor lesions from functionally relevant motor cortex and fibers in patients undergoing an operation. As such, the study was based on a multimodal imaging approach by the coregistered integration of the following: 1) MR imaging data for anatomically defining lesion extent (T2WI and T1WI) and allowing structural analysis by DTI tractography; 2) O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (FET)-PET for outlining the metabolic extent of the tumor because FET is the most evaluated ¹⁸F-labeled amino acid for PET of brain tumors, in particular in treatment planning and monitoring^22–25; and 3) nTMS data for a functional definition of the M1 region and allowing nTMS-based DTI tractography. We hypothesized the following: 1) The integration of FET-PET and nTMS data advances the preoperative evaluation of motor impairment more than with MR imaging alone by contrast-enhanced T1WI (T1-CE), T2WI, and DTI; and 2) lesional signal within primary motor functional tissue as depicted by the multimodal approach may then serve as a potential predictive imaging marker for motor function outcome.