Changes in the Thalamus in Atypical Parkinsonism Detected Using Shape Analysis and Diffusion Tensor Imaging

BACKGROUND AND PURPOSE:The thalamus is interconnected with the nigrostriatal system and cerebral cortex and has a major role in cognitive function and sensorimotor integration. The purpose of this study was to determine how regional involvement of the thalamus differs among Parkinson disease, progressive supranuclear palsy, and corticobasal syndrome.MATERIALS AND METHODS:Nine patients with Parkinson disease, 5 with progressive supranuclear palsy, and 6 with corticobasal syndrome underwent 3T MR imaging along with 12 matched, asymptomatic volunteers by using a protocol that included volumetric T1 and diffusion tensor imaging. Acquired data were automatically processed to delineate the margins of the motor and nonmotor thalamic nuclear groups, and measurements of ADC were calculated from the DTI data within these regions. Thalamic volume, shape, and ADC were compared across groups.RESULTS:Thalamic volume was smaller in the progressive supranuclear palsy and corticobasal syndrome groups compared with the Parkinson disease and control groups. Shape analysis revealed that this was mainly due to the diminished size of the lateral thalamus. Overall, ADC measurements were higher in the progressive supranuclear palsy group compared with both the Parkinson disease and control groups, and anatomic subgroup analysis demonstrated that these changes were greater within the motor regions of the thalamus in progressive supranuclear palsy and corticobasal degeneration.CONCLUSIONS:Reduced size and increased ADC disproportionately involve the lateral thalamus in progressive supranuclear palsy and corticobasal syndrome, consistent with selective neurodegeneration and atrophy in this region. Because these findings were not observed in Parkinson disease, they may be more specific markers of tau-related neurodegeneration.

The neurodegenerative movement disorders Parkinson disease (PD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) are distinguished postmortem by differing histologic abnormalities and regional patterns of neuropathologic changes. PSP and corticobasal syndrome (CBS) exhibit neuronal and glial cytoplasmic inclusions from accumulation of highly phosphorylated microtubule-associated tau protein, which is not evident in PD.^1–3 Paralleling these differences, typical clinical phenotypes help to distinguish these disorders. However, classic presentations are consistent only in advanced disease, and misdiagnosis is frequent in patients with early symptoms.^4,5 The diagnosis of CBD is particularly problematic⁶; for this reason, the term “corticobasal syndrome” is applied in lieu of CBD to convey the fact that disorders including Alzheimer disease, certain variants of frontotemporal lobar degeneration, and prion disease can present similarly.Various observations on MR imaging have been reported to differentiate PD, PSP, and CBD. Alterations in the shape or volume of several subcortical brain regions correlate with gross inspection of the brain in pathologically confirmed cases.⁷ However, such changes are subject to observer bias and are reliably found only in late disease. Unbiased approaches by using voxel-based morphometry and automated segmentation have also been applied with some success.^8–13 DTI studies have revealed increased diffusivity within the superior cerebellar peduncles in PSP,^14–16 along with more widespread changes within supratentorial white matter.^17,18 A number of groups have also described alterations in deep gray matter diffusion. For example, measurements of ADC are elevated within the putamen in up to 90% of patients with atypical parkinsonism but not significantly different from controls in patients with PD.^16,19The shared anatomic involvement of the basal ganglia and other brain regions in these disorders likely contributes to their frequent clinical overlap. Few studies have focused specifically on the thalamus, which, through the nigrostriatal system and thalamocortical circuits, plays a major role in cognition and sensorimotor integration. Alterations in thalamic volume have not been shown in prior studies of CBS, but significantly lower thalamic volume has been observed in PSP compared with both patients with PD²⁰ and controls.^10,20 Diminished volume by itself does not provide insight into how separate nuclear groups within the thalamus are selectively affected, however. One study suggested that thalamic shape differs between subjects with PD and healthy elders, though these changes were challenging to interpret because there was multifocal involvement over the entire surface of the thalamus without a corresponding difference in volume.²¹ Using DTI, Erbetta et al²² measured higher ADC within the anterior and lateral thalami in PSP and CBS compared with controls, but their analysis was based on relatively imprecise atlas-based estimates of nuclear boundaries.²²We hypothesized that regional thalamic morphology and tissue microstructure, measured with volumetric T1-weighted MR imaging and DTI, respectively, would be different in patients with PSP and CBS compared with patients with PD and controls. Using fully automated analysis of 3T T1 and DTI data, we evaluated thalamic shape and diffusion within motor and nonmotor thalamic nuclear groups and compared these measurements in patients with CBS, PSP, and PD and in healthy control subjects.     

Aneurysmal Subarachnoid Hemorrhage Causes Injury of the Ascending Reticular Activating System: Relation to Consciousness

BACKGROUND AND PURPOSE:Little is known about the pathogenetic mechanism of impaired consciousness following subarachnoid hemorrhage. Using diffusion tensor imaging, we attempted to investigate the presence of injury of the lower portion of the ascending reticular activating system between the pontine reticular formation and the intralaminar thalamic nuclei, and the relation between this injury and consciousness level in patients with SAH.MATERIALS AND METHODS:We recruited 24 consecutive patients with spontaneous SAH following aneurysmal rupture and 21 healthy control subjects. Consciousness level was rated by using the Glasgow Coma Scale. Using diffusion tensor tractography, we reconstructed the lower portion of the ascending reticular activating system between the pontine reticular formation and the intralaminar thalamic nuclei. Values of fractional anisotropy, apparent diffusion coefficient, and tract number of the ascending reticular activating system were measured.RESULTS:A significant difference in the tract number was observed between the patient and control groups (P < .05); however, there was no significant difference in terms of fractional anisotropy and apparent diffusion coefficient values (P > .05). In addition, regarding the tract number of the patient group, the Glasgow Coma Scale showed strong positive correlations with the tract number on the more affected side (r = 0.890, P < .05), the less affected side (r = 0.798, P < .05), and both sides (r = 0.919, P < .05), respectively.CONCLUSIONS:We found injury of the lower portion of the ascending reticular activating system between the pontine reticular formation and the thalamus in patients with SAH. In addition, we observed a close association between injury of the lower portion of the ascending reticular activating system and impaired consciousness in patients with SAH.

Subarachnoid hemorrhage, which occurs by extravasation of blood into the subarachnoid space covering the central nervous system, comprises 5% of all cases of stroke. The average fatality rate in patients with SAH is 51%.^1,2 Most deaths occur within 2 weeks after SAH, especially 25% within 24 hours, with approximately one-third of survivors needing life-long care.^1,2 Various neurologic complications are known to occur in >50% of survivors with SAH, and impaired consciousness is a common neurologic complication.² Two-thirds of patients with SAH have been reported to show impaired consciousness in the acute stage, and loss of consciousness is a powerful predictive factor for a poor neurologic outcome in patients with SAH.^2,3 However, the pathogenetic mechanism of impaired consciousness following SAH has not been clearly elucidated so far.⁴Human consciousness consists of arousal and awareness, which is accomplished by action of the pathway known as the ascending reticular activating system (ARAS).^5–7 The ARAS is a complex neural network connecting from the reticular formation of the brain stem to the cerebral cortex via excitatory relays in the intralaminar nuclei of the thalamus; therefore, accurate assessment of the ARAS plays an important role in the diagnosis and management of patients with impaired consciousness.^5–8 Successful evaluation of the ARAS has been limited despite many attempts by using conventional MR imaging, functional neuroimaging, electrophysiologic assessments, MR spectroscopy, and positron-emission tomography.^9–11By contrast, diffusion tensor tractography, which is derived from diffusion tensor imaging, has enabled 3D reconstruction and estimation of the ARAS in the healthy human brain.^5,6 In addition, a few studies have reported injury of the ARAS in patients with traumatic brain injury and hypoxic-ischemic brain injury by using diffusion tensor tractography.^12,13 However, no study on injury of the ARAS in patients with SAH has been reported, to our knowledge. In this study, we hypothesized that injury of the lower portion of the ARAS between the reticular formation of the brain stem and the intralaminar thalamic nuclei would be observed in patients with spontaneous SAH and that injury of the lower ARAS might be correlated with consciousness level.In the current study using DTI, we attempted to investigate the presence of injury of the lower portion of the ARAS between the pontine reticular formation and the intralaminar thalamic nuclei and the relation between this injury and consciousness level in patients with SAH following aneurysmal rupture at the chronic stage >3 weeks after onset.     

Increased Facet Fluid Predicts Dynamic Changes in the Dural Sac Size on Axial-Loaded MRI in Patients with Lumbar Spinal Canal Stenosis

BACKGROUND AND PURPOSE:Axial-loaded MR imaging, which simulates the spinal canal in a standing position, demonstrates reductions of the dural sac cross-sectional area in patients with lumbar spinal canal stenosis. However, there has been no useful conventional MR imaging finding for predicting a reduction in the dural sac cross-sectional area on axial-loaded MR imaging. Previous studies have shown that increased facet fluid is associated with the spinal instability detected during positional changes. The purpose of this study was to analyze the correlations between facet fluid and dynamic changes in the dural sac cross-sectional area on axial-loaded MR imaging.MATERIALS AND METHODS:In 93 patients with lumbar spinal canal stenosis, the dural sac cross-sectional area was measured by using axial images of conventional and axial-loaded MR imaging. Changes in the dural sac cross-sectional area induced by axial loading were calculated. The correlation between the facet fluid width measured on conventional MR imaging and the change in dural sac cross-sectional area was analyzed. The change in the dural sac cross-sectional area was compared between the intervertebral levels with and without the facet fluid width that was over the cutoff value determined in this study.RESULTS:The dural sac cross-sectional area was significantly smaller on axial-loaded MR imaging than on conventional MR imaging. The facet fluid width significantly correlated with the change in the dural sac cross-sectional area (r = 0.73, P < .001). The change in the dural sac cross-sectional area at the intervertebral level with the facet fluid width over the cutoff value was significantly greater than that at the other level.CONCLUSIONS:The increased facet fluid on conventional MR imaging is highly predictive of the dynamic reduction of dural sac cross-sectional area detected on axial-loaded MR imaging in the clinical assessment of lumbar spinal canal stenosis.

MR imaging is widely used for the clinical assessment of degenerative lumbar spinal diseases. In evaluating the severity of spinal canal narrowing, the dural sac cross-sectional area (DCSA) is frequently measured by using axial MR images.^1–6 However, conventional MR imaging is performed with the patient in the supine position, and the DCSA may be larger in this position than in the standing position.^3,4,7 Hence, conventional MR imaging carries a risk of underestimating the severity of spinal canal narrowing.^3,8Recently, the clinical usefulness of axial-loaded MR imaging for assessing patients with lumbar spinal canal stenosis (LSCS) has been reported.^3,4 With axial-loaded MR imaging, physiologically normal weight-bearing conditions in the upright position can be simulated by using a compression device with the patient in the supine position. Axial-loaded MR imaging may induce a significant reduction in the DCSA and potentially show additional imaging findings that cannot be acquired on conventional MR imaging.^3,4,6,8 The DCSA on axial-loaded MR imaging has been reported to correlate with the severity of clinical symptoms in patients with LSCS.⁹ Furthermore, previous studies have demonstrated that a dynamic decrease in the DCSA induced by axial loading increases the diagnostic specificity of spinal canal narrowing and influences the indications for surgical treatment.^4,8,10,11 Therefore, evaluating the degree of spinal canal narrowing on axial-loaded MR imaging is beneficial for achieving a more accurate diagnosis and selecting the optimal treatment. However, no reliable imaging findings on conventional MR imaging predict the dynamic reduction in the DCSA.Many previous studies have shown that the morphology of the facet joints is associated with the segmental motion and instability of the lumbar spine detected during positional changes in the patient.^12–15 Most interesting, recent studies have suggested that increased fluid signals in the facet joint on conventional MR images predict instability of the lumbar spine.^16–19 Therefore, in the present study, we hypothesized that increased facet fluid signals on conventional MR images may be correlated with significant changes in the DCSA on axial-loaded MR images because the lumbar spinal canal is more likely to be affected by axial loading if the lumbar spine is unstable.To the best of our knowledge, no previous studies have investigated the correlation between the facet fluid width and dynamic changes in the DCSA induced by axial loading. The purpose of this study was thus to analyze the correlation between the facet fluid width and dynamic changes in the DCSA detected by using axial-loaded MR imaging in patients with LSCS.     

Identification of the Inflow Zone of Unruptured Cerebral Aneurysms: Comparison of 4D Flow MRI and 3D TOF MRA Data

BACKGROUND AND PURPOSE:The hemodynamics of the inflow zone of cerebral aneurysms may be a key factor in coil compaction and recanalization after endovascular coil embolization. We performed 4D flow MR imaging in conjunction with 3D TOF MRA and compared their ability to identify the inflow zone of unruptured cerebral aneurysms.MATERIALS AND METHODS:This series comprised 50 unruptured saccular cerebral aneurysms in 44 patients. Transluminal color-coded 3D MRA images were created by selecting the signal-intensity ranges on 3D TOF MRA images that corresponded with both the luminal margin and the putative inflow.RESULTS:4D flow MR imaging demonstrated the inflow zone and yielded inflow velocity profiles for all 50 aneurysms. In 18 of 24 lateral-projection aneurysms (75%), the inflow zone was located distally on the aneurysmal neck. The maximum inflow velocity ranged from 285 to 922 mm/s. On 4D flow MR imaging and transluminal color-coded 3D MRA studies, the inflow zone of 32 aneurysms (64%) was at a similar location. In 91% of aneurysms whose neck section plane angle was <30° with respect to the imaging section direction on 3D TOF MRA, depiction of the inflow zone was similar on transluminal color-coded 3D MRA and 4D flow MR images.CONCLUSIONS:4D flow MR imaging can demonstrate the inflow zone and provide inflow velocity profiles. In aneurysms whose angle of the neck-section plane is obtuse vis-a-vis the imaging section on 3D TOF MRA scans, transluminal color-coded 3D MRA may depict the inflow zone reliably.

Although endovascular coil embolization has become a major tactic to address cerebral aneurysms, recanalization or recurrence, which may result in rebleeding, are important problems. Recanalization was reported in 6.1%–39.8% of patients who had undergone endovascular treatment,^1–6 and a meta-analysis found that 20.8% of treated aneurysms recurred.³ The rate of rerupture after endovascular treatment for ruptured aneurysms has ranged from 0.11% to 5.3%,^1,4,6 and the rupture rate in the first year after coil embolization was reported as 2.5%⁷ and 2.2%.⁸ Because hemodynamics acting on the aneurysmal inflow zone may play a key role in the development of coil compaction or recanalization after endovascular coil embolization, the aneurysmal inflow zone must be packed densely to preserve the durability of aneurysm obliteration and to prevent rerupture.^9–15The inflow through the aneurysmal neck into the dome can be seen on 3D TOF MRA images.^13,16,17 Satoh et al,^16,17 who used conventional 3D TOF MRA techniques to select threshold ranges based on the signal intensity of the volume-rendering data, determined the spatial signal-intensity distribution in aneurysms. They developed transluminal color-coded 3D MRA (TC 3D MRA) to improve visualization of the aneurysmal inflow. More recently, 4D flow MR imaging based on time-resolved 3D cine phase-contrast MR imaging techniques was used to evaluate the hemodynamics of cerebral aneurysms.^18–27 However, 4D flow MR imaging requires additional time for data acquisition, and TC 3D MRA may be a convenient alternative to 4D flow MR imaging for identifying the aneurysmal inflow zone.Here, we compared the ability of 4D flow MR imaging and TC 3D MRA to identify the inflow zone of cerebral aneurysms.     

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.     

Identifying Corticothalamic Network Epicenters in Patients with Idiopathic Generalized Epilepsy

BACKGROUND AND PURPOSE:Corticothalamic networks are considered core pathologic substrates for idiopathic generalized epilepsy; however, the predominant epileptogenic epicenters within these networks are still largely unknown. The current study aims to identify these epicenters by resting-state functional connectivity.MATERIALS AND METHODS:To identify epicenters within the corticothalamic networks in idiopathic generalized epilepsy, we retrospectively studied a large cohort of patients with this condition (n = 97) along with healthy controls (n = 123) by resting-state functional MR imaging. The thalamus was functionally divided into subregions corresponding to distinct cortical lobes for 5 parallel corticothalamic networks. The functional connectivity between each voxel in the cortical lobe and the corresponding thalamic subregion was calculated, and functional connectivity strength was used to evaluate the interconnectivity of voxels in the cortex and thalamus.RESULTS:The projection of 5 cortical lobes to the thalamus is consistent with previous histologic findings in humans. Compared with controls, patients with idiopathic generalized epilepsy showed increased functional connectivity strength in 4 corticothalamic networks: 1) the supplementary motor area, pulvinar, and ventral anterior nucleus in the prefrontal-thalamic network; 2) the premotor cortex and ventrolateral nucleus in motor/premotor-thalamic networks; 3) the visual cortex, posterior default mode regions, and pulvinar in parietal/occipital-thalamic networks; and 4) the middle temporal gyrus in the temporal-thalamic network.CONCLUSIONS:Several key nodes were distinguished in 4 corticothalamic networks. The identification of these epicenters refines the corticothalamic network theory and provides insight into the pathophysiology of idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) is a common subtype of epilepsy involving abnormally synchronized generalized spike-wave discharges (GSWDs) rapidly propagating to distributed networks.¹ Various theories have been proposed to explain the origin and mechanism of generalized seizures²; the corticothalamic network has been suggested as a preferred target for the modification or elimination of seizure discharges.^3,4There is substantial evidence that dysfunction in the corticothalamic circuitry contributes to the pathogenesis of generalized seizures.^3,4 Hemodynamic changes associated with GSWDs have been consistently observed in the thalamus and default mode areas.⁵ Recently, corticothalamic interactions in generalized epilepsy have been characterized by morphometric covariance,⁶ functional and anatomic connectivity,^7,8 and causal influence.⁹ In particular, corticothalamic connections (parcellated through probabilistic tractography) showed abnormal functional connectivity in juvenile myoclonic epilepsy.⁷ However, little attention has been paid to the functional topographic pathways linking distinct cortical areas and specific thalamic nuclei.^10,11 These projections likely have distinct roles in the mechanism of GSWDs,¹² so it is essential to investigate corticothalamic functional networks in generalized epilepsy. More precisely, characterizing epicenters within each network may facilitate the development of targeted surgical interventions (eg, deep brain stimulation) that selectively disrupt seizures and ultimately improve the clinical treatment of IGE.⁴It was recently demonstrated that resting-state functional connectivity can reveal distinct corticothalamic networks¹³ analogous to classic histologic parcellation.¹⁰ As in previous investigations,^14–16 a similar approach was adopted here to identify corticothalamic networks. We hypothesized that the functional synchronization of corticothalamic networks is altered in patients with IGE. To localize epicenters within these networks, we conducted a voxelwise comparison of network functional connectivity between patients and controls.     

Imaging Findings in MR Imaging–Guided Focused Ultrasound Treatment for Patients with Essential Tremor

BACKGROUND AND PURPOSE:MR imaging–guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue. The goal of this study was to describe MR imaging findings pre- and post-ventralis intermedius nucleus lesioning by MR imaging–guided focused sonography as a treatment for essential tremor and to determine whether there was an association between these imaging features and the clinical response to MR imaging–guided focused sonography.MATERIALS AND METHODS:Fifteen patients with medication-refractory essential tremor prospectively gave consent; were enrolled in a single-site, FDA-approved pilot clinical trial; and were treated with transcranial MR imaging–guided focused sonography. MR imaging studies were obtained on a 3T scanner before the procedure and 24 hours, 1 week, 1 month, and 3 months following the procedure.RESULTS:On T2-weighted imaging, 3 time-dependent concentric zones were seen at the site of the focal spot. The inner 2 zones showed reduced ADC values at 24 hours in all patients except one. Diffusion had pseudonormalized by 1 month in all patients, when the cavity collapsed. Very mild postcontrast enhancement was seen at 24 hours and again at 1 month after MR imaging–guided focused sonography. The total lesion size and clinical response evolved inversely compared with each other (coefficient of correlation = 0.29, P value = .02).CONCLUSIONS:MR imaging–guided focused sonography can accurately ablate a precisely delineated target, with typical imaging findings seen in the days, weeks, and months following the treatment. Tremor control was optimal early when the lesion size and perilesional edema were maximal and was less later when the perilesional edema had resolved.

MR imaging–guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue rapidly under closed-loop image guidance and control throughout all steps of the intervention process. MR imaging allows precise intraprocedural localization of the ablation target, verification of safety margins for the sonography treatment, and real-time monitoring of thermal ablation dynamics.^1–7 MR imaging–guided focused sonography is now accepted in the treatment of soft-tissue disorders, including prostate cancer and uterine fibroids. Intracranial applications for brain tumors^8,9 and neuropathic pain syndromes^10,11 are currently under investigation. More recently, MR imaging–guided focused sonography was tested in a clinical trial as a treatment for essential tremor.Essential tremor is a common and disabling movement disorder with an estimated prevalence of 0.3%–5.55%.^12–17 Patients with essential tremor may suffer more from the mental effects on quality of life, such as lower perceived health status,¹⁸ than from actual physical symptoms.¹⁹ Essential tremor may be medically refractory: up to 30% of patients do not respond to first-line therapy and may consider surgical options.²⁰ Improved imaging and refined electrophysiologic localization have demonstrated that the ventralis intermedius nucleus (Vim) of the thalamus is the most effective target. The ventralis intermedius nucleus was the target for the MR imaging–guided focused sonography treatment in the clinical trial mentioned above.The goal of this study was to describe findings on MR imaging both pre- and post-Vim lesioning by MR imaging–guided focused sonography as a treatment for essential tremor in the 15 patients enrolled in the trial and to determine whether there was an association between these imaging features, the number and/or energy of sonications, and the clinical response to MR imaging–guided focused sonography.     

Visualization of the Medial and Lateral Geniculate Nucleus on Phase Difference Enhanced Imaging

BACKGROUND AND PURPOSE:The precise identification and measurement of the medial geniculate nucleus and lateral geniculate nucleus on MR imaging remain technically challenging because the thalamic nuclei are small structures. We compared the visualization of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging with 3D high-resolution phase imaging, 2D-T2WI, STIR, proton attenuation–weighted imaging, and DTI acquired at 3T. We also measured the volume and height of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging.MATERIALS AND METHODS:Phase difference enhanced, 2D-T2-weighted, STIR, proton attenuation–weighted, and DTI were acquired on a 3T MR imaging unit in 10 healthy volunteers. Two neuroradiologists recorded the qualitative visualization scores of the medial geniculate nucleus and lateral geniculate nucleus, specifically the identification of their boundaries, for all images. Measurement differences were assessed with the Wilcoxon signed rank test. The volume and height of the medial geniculate nucleus and lateral geniculate nucleus were measured on phase difference enhanced imaging and compared with previously reported values.RESULTS:The qualitative visualization scores of the lateral geniculate nucleus and medial geniculate nucleus were significantly higher on phase difference enhanced images than on T2-weighted, proton attenuation–weighted, STIR, or DTI (P < .05). On phase difference enhanced imaging, the medial geniculate nucleus and lateral geniculate nucleus were bordered by low-intensity structures: the cerebral peduncle, the origin of the optic radiation, and the superior and inferior quadrigeminal brachia. The volume of the medial geniculate nucleus and lateral geniculate nucleus varied from 74.0 to 183.75 mm³ (mean, 129.0 ± 34.7 mm³) and from 96.5 to 173.75 mm³ (mean, 135.2 ± 28.0 mm³), respectively.CONCLUSIONS:For the depiction of the medial geniculate nucleus and lateral geniculate nucleus on 3T MR imaging, phase difference enhanced imaging is superior to conventional MR imaging. The medial geniculate nucleus and lateral geniculate nucleus volumes vary among individuals.

The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are the specific thalamic nuclei that relay the auditory and optic pathways, respectively. The triangular LGN is located in the posterior region of the thalamus. It is bordered anteriorly by the cerebral peduncle and the optic tract and posteriorly by the origin of the optic radiation. The oval MGN, with its long axis directed forward and laterally just medial to the LGN, is bordered anteriorly by the inferior quadrigeminal brachium and posteriorly by the superior quadrigeminal brachium. There is increasing interest in assessing the MGN and LGN in healthy subjects and in patients with ophthalmic diseases such as glaucoma.^1–6 However, current imaging methods for identifying the MGN and LGN vary, and imaging findings are inconsistent.Technical advances in neuroimaging facilitate the study of subcortical structures in vivo. Phase difference enhanced (PADRE) imaging yields a high tissue contrast that delineates specific white matter tracts and intracortical structures.^7–9 On high-spatial-resolution 3T PADRE images, small structures, including the central tegmental tract, the medial and dorsal longitudinal fascicules, and the stria of Gennari, which are difficult to appreciate on conventional MR images, are delineated.^7,8 Also, the contrast between specific white matter structure (eg, the optic radiation) is higher on PADRE than on conventional MR images.⁷We compared visualization of the MGN and LGN on PADRE, 2D-T2-weighted, STIR, proton attenuation–weighted (PD), and DTI acquired at 3T. We also measured the volume and height of the MGN and LGN on PADRE images.     

Comparison of High-Resolution MR Imaging and Digital Subtraction Angiography for the Characterization and Diagnosis of Intracranial Artery Disease

BACKGROUND AND PURPOSE:High-resolution MR imaging has recently been introduced as a promising diagnostic modality in intracranial artery disease. Our aim was to compare high-resolution MR imaging with digital subtraction angiography for the characterization and diagnosis of various intracranial artery diseases.MATERIALS AND METHODS:Thirty-seven patients who had undergone both high-resolution MR imaging and DSA for intracranial artery disease were enrolled in our study (August 2011 to April 2014). The time interval between the high-resolution MR imaging and DSA was within 1 month. The degree of stenosis and the minimal luminal diameter were independently measured by 2 observers in both DSA and high-resolution MR imaging, and the results were compared. Two observers independently diagnosed intracranial artery diseases on DSA and high-resolution MR imaging. The time interval between the diagnoses on DSA and high-resolution MR imaging was 2 weeks. Interobserver diagnostic agreement for each technique and intermodality diagnostic agreement for each observer were acquired.RESULTS:High-resolution MR imaging showed moderate-to-excellent agreement (interclass correlation coefficient = 0.892–0.949; κ = 0.548–0.614) and significant correlations (R = 0.766–892) with DSA on the degree of stenosis and minimal luminal diameter. The interobserver diagnostic agreement was good for DSA (κ = 0.643) and excellent for high-resolution MR imaging (κ = 0.818). The intermodality diagnostic agreement was good (κ = 0.704) for observer 1 and moderate (κ = 0.579) for observer 2, respectively.CONCLUSIONS:High-resolution MR imaging may be an imaging method comparable with DSA for the characterization and diagnosis of various intracranial artery diseases.

Intracranial artery disease (ICAD) is one of the major causes of ischemic stroke and neurologic symptoms.^1–3 ICAD generally presents with intracranial artery stenosis on luminal evaluation, even though it includes various ICADs, such as atherosclerosis, dissection, Moyamoya disease, and vasculitis. The degree of stenosis has been the most common and important characteristic for evaluating ICAD and determining the treatment options.^4,5Luminal angiography, such as digital subtraction angiography, CT angiography, and MR angiography, has been widely used and has functioned successfully for the evaluation of stenosis and the diagnosis of ICAD. Among these methods, DSA is thought to be the criterion standard tool compared with the other modalities because it depicts luminal geometric shapes and hemodynamic information with higher resolution.^6–8 However, DSA has several limitations. It only depicts the luminal morphology and not the vessel walls directly, and many diseases share nonspecific luminal findings. Because DSA is also an invasive procedure with the risk of neurologic complications and radiation exposure, it is not suitable for screening or serial examinations.^9–11 Accordingly, CTA and MRA have been commonly used as the minimally invasive method to diagnose and differentiate intracranial artery disease in the clinical field, though they have more drawbacks in the luminal evaluation to DSA.High-resolution MR imaging (HR-MR) has recently been introduced as a minimally invasive and promising advanced imaging technique for directly depicting the intracranial arterial wall.^12,13Although HR-MR evaluates and differentiates various ICADs with the direct depiction of arterial walls and multicontrast images^6,14–20 that may correlate with luminal angiography,^8,21,22 the usefulness and value of HR-MR compared with luminal angiography are still unclear. Only a few studies presented a comparison or correlation between DSA and HR-MR,^8,13,23 and these studies showed a good correlation regarding the degree of stenosis^8,23 and HR-MR features beyond DSA.¹³ However, the observations were based on single vascular pathology or a single cerebral artery (middle cerebral artery, basilar artery) or a small sample size (n = 9).In our study, we compared HR-MR with DSA in the characterization and diagnosis of various ICADs. We hypothesized that HR-MR may be an imaging method comparable with DSA for the characterization and diagnosis of ICAD.     

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.     

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.     

Manual Segmentation of MS Cortical Lesions Using MRI: A Comparison of 3 MRI Reading Protocols

BACKGROUND AND PURPOSE:Double inversion recovery has been suggested as the MR imaging contrast of choice for segmenting cortical lesions in patients with multiple sclerosis. In this study, we sought to determine the utility of double inversion recovery for cortical lesion identification by comparing 3 MR imaging reading protocols that combine different MR imaging contrasts.MATERIALS AND METHODS:Twenty-five patients with relapsing-remitting MS and 3 with secondary-progressive MS were imaged with 3T MR imaging by using double inversion recovery, dual fast spin-echo proton-density/T2-weighted, 3D FLAIR, and 3D T1-weighted imaging sequences. Lesions affecting the cortex were manually segmented by using the following 3 MR imaging reading protocols: Protocol 1 (P1) used all available MR imaging contrasts; protocol 2 (P2) used all the available contrasts except for double inversion recovery; and protocol 3(P3) used only double inversion recovery.RESULTS:Six hundred forty-three cortical lesions were identified with P1 (mean = 22.96); 633, with P2 (mean = 22.6); and 280, with P3 (mean = 10). The counts obtained by using P1 and P2 were not significantly different (P = .93). The counts obtained by using P3 were significantly smaller than those obtained by using either P1 (P < .001) or P2 (P < .001). The intraclass correlation coefficients were P1 versus P2 = 0.989, P1 versus P3 = 0.615, and P2 versus P3 = 0.588.CONCLUSIONS:MR imaging cortical lesion segmentation can be performed by using 3D T1-weighted and 3D FLAIR images acquired with a 1-mm isotropic voxel size, supported by conventional T2-weighted and proton-density images with 3-mm-thick sections. Inclusion of double inversion recovery in this multimodal reading protocol did not significantly improve the cortical lesion identification rate. A multimodal approach is superior to using double inversion recovery alone.

Multiple sclerosis is an inflammatory and neurodegenerative disease that affects both the white matter and gray matter of the central nervous system. Postmortem immunohistochemical characterization of cortical lesions (CLs) has allowed the identification of a substantial burden of cortical GM lesions in patients with long-standing MS.^1–5 However, the prevalence of cortical lesions at earlier stages of MS is underexplored.⁶ As a result, an efficient, standardized MR imaging protocol for segmentation of CLs in early-stage MS has become an important research goal. Double inversion recovery (DIR) MR imaging has generally been selected because it enhances the conspicuity of GM by suppressing unwanted signal from both WM and CSF. However, DIR images have a low signal-to-noise ratio due to the application of 2 inversion pulses. They are also prone to hyperintense vascular artifacts, which can confound CL identification.^7–14In 2011, an international panel of experts formulated consensus recommendations for scoring CLs at 1.5T and 3T by using DIR.¹¹ As part of the recommendations, they noted that in the future, the additional use of other MR imaging contrasts (T1-weighted, T2-weighted, or fluid-attenuated inversion recovery images) in combination with DIR could improve the detection of cortical lesions by reducing the number of false-positives and false-negatives. Several groups have since reported on such multicontrast approaches for segmenting CLs. Examples include the following: 1) CL segmentation performed by using a single MR imaging contrast followed by subsequent verification of lesion labels on other contrasts¹³; 2) CL segmentation performed independently by using 2 different MR imaging contrasts, where a tight correlation between the counts is considered evidence that each MR imaging contrast yields counts proportional to the real lesion load¹⁵; 3) CL segmentation performed by using a single MR imaging contrast with the results subsequently reviewed by a second (more experienced) rater who uses other contrasts to resolve ambiguities/potential false-positives¹⁶; and 4) CL segmentation performed independently for each independent contrast, and then each count compared with the counts obtained from the other MR imaging contrasts to determine which one detects the highest number of lesions.¹⁷ The variability among these methods has led to difficulty in developing a standardized CL segmentation protocol.¹¹ Consequently, a major goal of this work was to identify a robust, multicontrast CL segmentation protocol that could be used with more generally available MR imaging pulse sequences at clinically accessible magnetic field strengths.According to the consensus recommendations, only type I leukocortical and type II intracortical lesions should be considered for radiologic scoring¹¹ in MS. However, type I lesions affecting both the cortex and the juxtacortical white matter are often difficult to differentiate from purely juxtacortical lesions. Consequently, these lesions can be misclassified. Type II lesions are the smallest and affect the cortex without reaching either the pial or white matter boundaries. These lesions are also challenging to detect visually by using 1.5T or 3T MR imaging. Subpial lesions (type III and IV), extending from the pial boundary down to the white matter surface, are not considered within the consensus guidelines for MR imaging at 1.5 and 3T due to their low detectability at these clinical field strengths. Even with these simplifying assumptions in place, CL identification has been highly variable.^10,13,18,19 The prevalence of MR imaging–identified intracortical lesions ranges from 8.2% to 46% across different published reports.^{10,12,13,18,19} This variability may partially reflect the variable sensitivity of current MR imaging protocols but also may indicate the inherent variability of cortical lesion involvement across MS disease stages and individual patients. Support for this hypothesis is provided by histology studies in which the percentage of intracortical lesions (type II) also shows a wide range: 7%–31% and 17%–71% when we consider types I and type II combined.^{1–6,19,20,21}A significant aim of our study was to simplify and improve the process of manual cortical lesion segmentation when using multiple MR imaging contrasts derived from 3T MR imaging. We specifically strived to identify a lesion-segmentation method with reduced variability and reduced false-positive identifications. To do this, we avoided classification of cortical lesions into subtypes.     

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.     

Reduction of Oxygen-Induced CSF Hyperintensity on FLAIR MR Images in Sedated Children: Usefulness of Magnetization-Prepared FLAIR Imaging

BACKGROUND AND PURPOSE:Oxygen-induced CSF hyperintensity on FLAIR MR imaging is often observed in sedated children. This phenomenon can mimic leptomeningeal pathology and lead to a misdiagnosis. The purpose of this study was to investigate whether magnetization-prepared FLAIR MR imaging can reduce oxygen-induced CSF hyperintensity and improve image quality compared with conventional (non-magnetization-prepared) FLAIR MR imaging.MATERIALS AND METHODS:Bloch simulation for magnetization-prepared and non-magnetization-prepared FLAIR sequences was performed for tissue contrast. We retrospectively reviewed 85 children with epilepsy who underwent MR imaging under general anesthesia with supplemental oxygen (41 with non-magnetization-prepared FLAIR and 44 with magnetization-prepared FLAIR). CSF hyperintensity was scored from 0 to 3 points according to the degree of CSF signal intensity and was compared between the 2 sequences. The contrast-to-noise ratios among GM, WM, and CSF were evaluated to assess general image quality from both sequences. To assess the diagnostic accuracy for hemorrhage, we reviewed an additional 25 patients with hemorrhage.RESULTS:Bloch simulation demonstrated that CSF hyperintensity can be reduced on magnetization-prepared FLAIR compared with non-magnetization-prepared FLAIR. CSF hyperintensity scores were significantly lower in magnetization-prepared FLAIR than in non-magnetization-prepared FLAIR (P < .01). The contrast-to-noise ratios for GM-WM, GM-CSF, and WM-CSF were significantly higher in magnetization-prepared FLAIR than in non-magnetization-prepared FLAIR (P < .05). Hemorrhage was clearly demarcated from CSF hyperintensity in the magnetization-prepared group (100%, 12/12) and non-magnetization-prepared group (38%, 5/13).CONCLUSIONS:Magnetization-prepared 3D-FLAIR MR imaging can significantly reduce oxygen-induced CSF artifacts and increase the tissue contrast-to-noise ratio beyond the levels achieved with conventional non-magnetization-prepared 3D-FLAIR MR imaging.

MR imaging is the diagnostic tool of choice in pediatric neurologic diseases because it has no ionizing radiation and is noninvasive. However, sedation is unavoidable if suitable MR images are sought because pediatric patients usually do not cooperate during long-duration scans.CSF hyperintensity on FLAIR MR images is frequently encountered in sedated children.^1–5 These artifacts cause a diagnostic dilemma because they can mimic hemorrhage, infection, and leptomeningeal seeding metastasis, which are all known to generate hyperintense CSF signals on FLAIR MR images.^6–9 Initially, CSF hyperintensity was attributed to anesthetic-induced T1-shortening, protein redistribution due to changes in the intravascular membrane permeability, hyperdynamic CSF pulsation due to altered vascular tone, and supplemental oxygen during anesthesia.^2–4,10 However, several studies have revealed that the most plausible cause of hyperintense CSF artifacts in FLAIR imaging is the administration of supplemental oxygen during anesthesia.^1,2,4,5,10Oxygen is a weak paramagnetic substance, which has 2 unpaired electrons that can cause a moderate increase in the T1 relaxation rate.^11,12 Studies have shown that the diffusional transfer of oxygen from blood to CSF and a consequent FLAIR MR signal increase depend on the inhaled oxygen concentration^1,2,4,13 and oxygen delivery methods.^3,103D-FLAIR imaging is based on the 3D TSE imaging technique that modulates a refocusing flip angle at the TSE echo-train to maintain relatively steady signal levels during a long train of echo signals, which can provide improved image sharpness, helpful in detecting small structures. Consequently, the relaxation-induced image blurring, partial volume effect, and specific absorption rate can be reduced allowing high-resolution 3D data acquisition at isotropic voxels during clinically feasible scan durations.¹⁴ 3D-FLAIR also provides increased SNR and reduces CSF pulsation artifacts compared with 2D FLAIR.^5,15–18 In magnetization-prepared (MP) 3D-FLAIR imaging, a dedicated magnetization preparation is implemented before typical inversion recovery, followed by TSE imaging, which is known to reduce unwanted T1-weighting and image TR.^19,20 Therefore, the purpose of this study was to compare magnetization-prepared 3D-FLAIR imaging with conventional (non-MP) 3D-FLAIR imaging in terms of the ability to reduce oxygen-induced CSF hyperintensity and improve image quality in sedated pediatric patients.     

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis

BACKGROUND AND PURPOSE:Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging–based iron-susceptibility measures.MATERIALS AND METHODS:Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.RESULTS:Compared with controls, patients showed reduced memory (P < .001) and processing speed (P = .02) and smaller putamen (P < .001), globus pallidus (P = .002), and thalamic volumes (P < .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (P = .003) and globus pallidus (P = .003). In patients only, thalamus (P < .001) and putamen (P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition.CONCLUSIONS:Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

Cognitive problems occur in 40%–65% of individuals with multiple sclerosis, predominantly affecting information processing speed and episodic memory.¹ Subcortical atrophy, particularly in the thalamus, is well-known to predict cognitive deficits in MS.² Elevated levels of iron accumulation in deep gray matter (DGM) nuclei in MS have also been reported using different iron-sensitive MR imaging measures, with studies focusing particularly on the large basal ganglia nuclei (caudate, putamen, globus pallidus [GP]), and the thalamus).³ Excess iron catalyzes production of free radicals, promoting neurodegeneration. This affects the DGM in both healthy aging and different CNS disorders.⁴ DGM iron accumulation in MS may be an epiphenomenon of structural atrophy caused by cell death,⁵ but others reported no relationships between DGM iron, global/regional brain volumes, or lesion load, suggesting potentially independent pathologies.⁶ The functional implications of DGM iron accumulation relative to other DGM pathologies in MS need further examination. Previous studies have examined some aspects of cognitive functions and DGM iron in MS with 4 different MR techniques.^5,7–11 Among the MR imaging measures used, only the gradient-echo transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) have been validated against postmortem iron assessment, both in non-MS^12,13 and in MS populations.^14,15Three MS studies assessed different aspects of cognition along with R2*.^5,10,11 In Khalil et al,⁵ R2* in the basal ganglia (but not in the thalamus) was related to processing speed in patients with clinically isolated syndrome and those with MS. In Pinter et al,¹⁰ a neuropsychological composite score of cognitive efficiency/processing speed (but not memory) of patients with clinically isolated syndrome and patients with MS was reported. This was predicted by R2* relaxation rates averaged across basal ganglia nuclei, along with caudate volume and T2 lesion load. Schmalbrock et al¹¹ recently cross-examined QSM and R2* measures against performance in 2 inhibitory cognitive tasks (a Stroop Task and an Eriksen Flanker Task) in patients with relapsing-remitting MS, imaged at 7T. Inhibition in the Flanker Task (but not the Stroop Task) was related to caudate and anterior putamen iron assessed with QSM, but performance in neither task was related to R2* measures. Thus, only 1 study¹¹ directly compared the cognitive correlates of R2* and QSM-based iron measures in MS, but it did not control for atrophy in the same DGM regions.The objective of our study was to determine whether cognition in MS, measured by the Brief Repeatable Battery of Neuropsychological Tests, is related to DGM iron accumulation measured with R2* and QSM at a high field strength (4.7T). The core hypothesis was that iron (R2* and QSM) in DGM nuclei correlates with decreased cognitive performance in MS, irrespective of atrophy.     

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.     

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.     

Inflow Jet Patterns of Unruptured Cerebral Aneurysms Based on the Flow Velocity in the Parent Artery: Evaluation Using 4D Flow MRI

BACKGROUND AND PURPOSE:Inflow jet characteristics may be related to aneurysmal bleb formation and rupture. We investigated the visualization threshold on the basis of the flow velocity in the parent artery to classify the inflow jet patterns observed on 4D flow MR imaging.MATERIALS AND METHODS:Fifty-seven unruptured aneurysms (24 bifurcation and 33 sidewall aneurysms) were subjected to 4D flow MR imaging to visualize inflow streamline bundles whose velocity exceeded visualization thresholds corresponding to 60%, 75%, and 90% of the maximum flow velocity in the parent artery. The shape of the streamline bundle was determined visually, and the inflow jet patterns were classified as concentrated, diffuse, neck-limited, and unvisualized.RESULTS:At the 75% threshold, bifurcation aneurysms exhibited a concentrated inflow jet pattern at the highest rate. At this threshold, the inflow jets were concentrated in 13 aneurysms (group C, 22.8%), diffuse in 18 (group D, 31.6%), neck-limited in 11 (group N, 19.3%), and unvisualized in 15 (group U, 26.3%). In 16 (28.1%) of the 57 aneurysms, the inflow jet pattern was different at various thresholds. Most inflow parameters, including the maximum inflow velocity and rate, the inflow velocity ratio, and the inflow rate ratio, were significantly higher in groups C and D than in groups N and U.CONCLUSIONS:The inflow jet pattern may depend on the threshold applied to visualize the inflow streamlines on 4D flow MR imaging. For the classification of the inflow jet patterns on 4D flow MR imaging, the 75% threshold may be optimal among the 3 thresholds corresponding to 60%, 75%, and 90% of the maximum flow velocity in the parent artery.

The inflow jets of cerebral aneurysms have been characterized as flow structures composed of strongly directed inflow with higher speeds than in other parts of the aneurysm.^1,2 Computational fluid dynamics analyses by using human cerebral aneurysm models suggested that inflow jets may be related to bleb formation and aneurysmal rupture.^3–5 Cebral et al³ reported that most blebs formed at sites where the inflow jet impacted the aneurysmal wall, and they qualitatively classified the inflow jets of ruptured and unruptured cerebral aneurysms into concentrated and diffuse inflow jets.^3–5 They found that most ruptured aneurysms featured concentrated inflow jets, while diffuse inflow jets tended to be seen in unruptured aneurysms.^4,5 This finding suggests that bleb formation and aneurysm rupture may be attributable to a degenerative change in the aneurysm wall exposed to the increased hemodynamic stress exerted by the inflow jet. Therefore, the assessment of inflow jet patterns and quantitative estimation of the inflow hemodynamics may contribute to a more precise prediction of the risk for bleb formation and aneurysm rupture.Computational fluid dynamics analysis uses human aneurysm models based on a number of assumptions and approximations regarding blood properties, vessel wall compliance, and flow conditions.^3–8 For the quantitative evaluation of the hemodynamics in real human cerebral aneurysms, 4D flow MR imaging, which is based on time-resolved 3D cine phase-contrast MR imaging techniques, has been used.^9–20 In this study, we investigated the visualization threshold on the basis of the flow velocity in the parent artery to classify the inflow jet patterns of unruptured cerebral aneurysms on 4D flow MR imaging. We applied different thresholds to visualize the inflow streamlines, evaluated the inflow jet patterns, and examined the relationship between the inflow jet pattern and the inflow hemodynamics.