TMEM119-positive microglia were increased in the brains of patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that has been reported to be affected by inflammatory cells, such as microglia and macrophages, through the concept of non-cell autonomous neuronal death. Resident microglia in the human brain and monocyte-derived macrophages (MoDM) infiltrating in tissues are difficult to distinguish. Therefore, the effects of microglia and MoDMs in ALS remain poorly understood. This study aimed to investigate the role of resident microglia and MoDMs in the pathogenesis of ALS using postmortem brain and spinal cord samples. The samples used for immunohistochemical analysis included 11 cases of sporadic ALS and 11 age-matched controls. We stained the cells with TMEM119 to detect resident microglia and CCR2 to detect MoDMs. In ALS cases, TMEM119-immunopositive resident microglia were abundant in the motor cortex and subcortical white matter (SWM) of the motor area, whereas CCR2-immunopositive MoDM was similar to control cases. In addition, the mean density of CD68-immunopositive cells in the SWM significantly correlated with the mean density of pTDP-43-positive GCIs. These results suggest that resident microglial activation plays an important role in the cerebral pathogenesis of ALS and may provide novel therapeutic strategies to target excessive activation of resident microglia in ALS.

Neuroimaging at 7 Tesla: a pictorial narrative review.

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders.

[Posterior Subthalamic Area, Pallidothalamic Tract, and Pedunculopontine Nucleus:Deep Brain Stimulation Targets for Parkinson's Disease and Essential Tremor].

This article reviews the stereotactic targets in the posterior subthalamic area(PSA), fields H1/H2 of Forel(pallidothalamic tract), and the pedunculopontine nucleus(PPN)to complement the preceding articles on stereotactic and functional neurosurgery for movement disorders in the present issue of No Shinkei Geka. Two regions within the subthalamus, the PSA and fields H1/H2 of Forel, are the revisited stereotactic targets to treat movement disorders. Currently, the PSA is often utilized to treat essential tremor and various types of tremor. Fields H1/H2 of Forel are investigated as a target for magnetic resonance-guided focused ultrasound to treat motor symptoms and motor complications in patients with Parkinson's disease. For the past twenty years, the PPN has been investigated to treat refractory gait freezing and fall in patients with Parkinson's disease. These revisited and novel targets may be utilized as substitutes and complements for the present standard stereotactic targets.

Thalamic Deep Brain Stimulation for Refractory Atypical Tremor after Encephalitis of Unknown Etiology: A Case Report.

Tremor associated with encephalitis is usually transient and rarely becomes chronic and refractory. Treatment for such tremor using deep brain stimulation (DBS) has not yet been reported. We report an uncommon case of chronic tremor after encephalitis of unknown etiology and its outcome treated with thalamic DBS. A 47-year-old man presented with a 6-month history of medically refractory tremor after non-infectious and probable autoimmune encephalitis. The patient showed an atypical mixture of resting, postural, kinetic, and intention tremor. The tremor significantly disabled the patient's activities of daily life (ADL). The patient underwent bilateral thalamic DBS surgery. DBS leads were placed to cross the border between the ventralis oralis posterior (Vop) nucleus and ventralis intermedius (Vim) nucleus of the thalamus. Stimulation of both the Vop and Vim using the bipolar contacts controlled the mixed occurrence of tremor. The ADL and performance scores on The Essential Tremor Rating Assessment Scale (TETRAS) improved from 47 to 0 and from 44 to 9, respectively. The therapeutic effects have lasted for 24 months. Administration of combined Vop and Vim DBS may control uncommon tremor of atypical etiology and phenomenology.

[A case of refractory generalized atonic seizure and hemifacial spasm with the possible causative pontocerebellar lesion].

The patient was a 35-year-old woman. At the age of 1, she had undergone resection and radiation therapy for neoplastic lesions in the pons. She had a history of gelastic seizures when she was in elementary school, and brief lapses of the neck and truncal muscular tone and convulsions on the left face occurred at the age of 23. After a generalized sharp wave in the ictal electroencephalogram and electromyogram recording, left orbicularis oris muscle contraction was observed followed by sudden cervical extensor atonia. Seizure propagation was noted in the cerebral cortex, left facial nerve nucleus, and brainstem reticular formation. In a simultaneous electroencephalography with functional MRI, the blood oxygen level-dependent effect related to generalized sharp waves was observed in the vicinity of brainstem lesions in addition to a decrease in bilateral frontal and parietal lobes signals, as detected in generalized seizures. These findings suggest that the lesion could be a part of the epilepsy network. Although most epileptic seizures are derived from the cerebral cortex, it is important to note that brainstem lesions are involved in seizures in the patient presented in this study.

Thigh muscle MRI findings in myopathy associated with anti-mitochondrial antibody.

INTRODUCTION: Myopathy associated with anti-mitochondrial antibody (AMA) has recently been characterized as a distinct type of idiopathic inflammatory myopathy. The purpose of this study is to evaluate the pattern of involvement in thigh muscles in AMA myopathy using MRI. METHODS: Six patients with AMA myopathy were identified and their muscle MRI findings evaluated. RESULTS: On thigh muscle MRI, all six patients showed high signal intensity with short-tau inversion recovery that reflected disease activity mostly in the adductor magnus, called a "cuneiform sign." Fatty degeneration was also prominent in the adductor magnus, as well as the semimembranosus muscles. DISCUSSION: These characteristic changes on MRI contrast with those of other inflammatory myopathies. From these observations, we concluded that the localization pattern of the inflammatory changes in muscle MRI can contribute to the diagnosis of AMA myopathy.

Phosphorylated NF-κB subunit p65 aggregates in granulovacuolar degeneration and neurites in neurodegenerative diseases with tauopathy.

Granulovacuolar degeneration (GVD) was originally reported in Alzheimer's disease (AD) and later found in aging brains. Pathologically, GVD is thought to be associated with the development of tauopathy, but the precise mechanism remains unknown. Previous studies have suggested that GVD contains proteins associated with an inflammatory signal. In this study, we examined phosphorylated p65 (pp65), which is the activated form of a subunit of nuclear factor-kappa B (NF-κB), in the hippocampus of 21 autopsied cases, including AD, amyotrophic lateral sclerosis cases with optineurin mutation (ALS-OPTN), and a variety of other neurodegenerative disorder cases and normal controls. In all cases, GVDs were immunopositive for pp65. The density of pp65-positive GVDs statistically correlated with that of casein kinase 1 delta (CK1δ), which is known as GVD marker. pp65 was also detected in neurites in AD and ALS-OPTN. The number of neurons with pp65-immunoreactive GVD was significantly higher in the AD group than in the non-AD group. Double immunostaining showed the colocalization of CK1δ and pp65. pp65-positive GVD was found in a neuron with AT8-positive neurofibrillary tangles. Moreover, pp65 was also found in neurites that were immunostained with phosphorylated tau, phosphorylated α-synuclein, or TDP-43 (transactivation response element DNA-binding protein 43 kDa). Therefore, the activation of the NF-κB pathway may be related to the pathology of GVD formation and dementia with tauopathy, including AD and ALS-OPTN. We propose that pp65 is useful as a GVD marker, and that the NF-κB pathway could be a therapeutic target not only for AD, but for age-related neurodegenerative diseases in general.

NLRP3 Inflammasome-Related Proteins Are Upregulated in the Putamen of Patients With Multiple System Atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia, and autonomic dysfunction. Microglial infiltration is an important mediator in MSA. The nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) inflammasome complex, comprising NLRP3, apoptotic speck protein containing a caspase recruitment domain (ASC), and cysteine aspartic acid protease 1 (Caspase 1), regulates microglial inflammation in several neurodegenerative diseases. However, its role in MSA remains unknown. This study aimed to investigate the role of the NLRP3 inflammasome in MSA. Immunohistochemical staining of postmortem brains from 11 cases of MSA, 5 of Parkinson disease, and 6 age-matched controls were assessed. The relationships among α-synuclein deposition, microglial infiltration, and NLRP3 inflammasome-related proteins (NLRP3, ASC, and Caspase 1) were quantitatively analyzed. Double-labeling immunofluorescence staining confirmed colocalization of NLRP3 inflammasome-related proteins and Cluster of Differentiation 68. We demonstrated that the density of microglia expressing NLRP3 inflammasome-related proteins was increased in the putamina of MSA cases and was significantly related to the deposition of phosphorylated α-synuclein-positive glial cytoplasmic inclusions, tyrosine hydroxylase-positive fiber loss, and gliosis of glial fibrillary acidic protein-positive astrocytes. Our study suggests that the NLRP3 inflammasome is significantly upregulated and correlates with the neurodegenerative process in MSA.

Amyotrophic Lateral Sclerosis after Receiving the Human Papilloma Virus Vaccine: A Case Report of a 15-year-old Girl.

We herein report a 15-year-old girl who developed rapid progressive muscle weakness soon after the third injection of a bivalent human papilloma virus (HPV) vaccine. Although immunotherapies were performed for possible vaccine-related disorders, she died of respiratory failure 14 months after the onset of the disease. A genetic analysis identified a heterozygous p.P525L mutation of the fused in sarcoma (FUS) gene, and a histopathological analysis was also consistent with FUS-associated amyotrophic lateral sclerosis (ALS) without any evidence of neuroinflammation. We concluded the diagnosis to be FUS-ALS, although we cannot completely rule out the possibility that the vaccination worked as a trigger.

Clinical impact of intraoperative CCEP monitoring in evaluating the dorsal language white matter pathway.

In order to preserve postoperative language function, we recently proposed a new intraoperative method to monitor the integrity of the dorsal language pathway (arcuate fasciculus; AF) using cortico-cortical evoked potentials (CCEPs). Based on further investigations (20 patients, 21 CCEP investigations), including patients who were not suitable for awake surgery (five CCEP investigations) or those without preoperative neuroimaging data (eight CCEP investigations including four with untraceable tractography due to brain edema), we attempted to clarify the clinical impact of this new intraoperative method. We monitored the integrity of AF by stimulating the anterior perisylvian language area (AL) by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. After tumor resection, single-pulse electrical stimuli were also applied to the floor of the removal cavity to record subcortico-cortical evoked potentials (SCEPs) at AL and PL in 12 patients (12 SCEP investigations). We demonstrated that (1) intraoperative dorsal language network monitoring was feasible even when patients were not suitable for awake surgery or without preoperative neuroimaging studies, (2) CCEP is a dynamic marker of functional connectivity or integrity of AF, and CCEP N1 amplitude could even become larger after reduction of brain edema, (3) a 50% CCEP N1 amplitude decline might be a cut-off value to prevent permanent language dysfunction due to impairment of AF, (4) a correspondence (<2.0 ms difference) of N1 onset latencies between CCEP and the sum of SCEPs indicates close proximity of the subcortical stimulus site to AF (<3.0 mm). Hum Brain Mapp 38:1977-1991, 2017. © 2017 Wiley Periodicals, Inc.

Paraneoplastic Limbic Encephalitis in a Human Epidermal Growth Factor Receptor-2-positive Gastric Cancer Patient Treated with Trastuzumab-combined Chemotherapy: A Case Report and Literature Review.

Paraneoplastic neurological syndromes (PNSs) are rare nervous system dysfunctions in cancer patients, which are primarily observed with small-cell lung cancer, gynecological cancer, and thymoma. We herein present an uncommon case of PNS in an anti-Hu antibody-positive patient with human epidermal growth factor receptor (HER)-2-positive gastric cancer (GC), who developed limbic encephalitis and a worsening cognitive function. Trastuzumab-combined chemotherapy was initiated and appeared to be partially effective for controlling the neurological symptoms and tumor volume. Chemotherapy failure eventually led to uncontrollable neurological symptoms. This is the first case demonstrating that trastuzumab-combined chemotherapy may be effective for controlling neurological symptoms of PNS in HER2-positive GC patients.

Epileptic network of hypothalamic hamartoma: An EEG-fMRI study.

OBJECTIVE: To investigate the brain networks involved in epileptogenesis/encephalopathy associated with hypothalamic hamartoma (HH) by EEG with functional MRI (EEG-fMRI), and evaluate its efficacy in locating the HH interface in comparison with subtraction ictal SPECT coregistered to MRI (SISCOM). METHODS: Eight HH patients underwent EEG-fMRI. All had gelastic seizures (GS) and 7 developed other seizure types. Using a general linear model, spike-related activation/deactivation was analyzed individually by applying a hemodynamic response function before, at, and after spike onset (time-shift model=-8-+4s). Group analysis was also performed. The sensitivity of EEG-fMRI in identifying the HH interface was compared with SISCOM in HH patients having unilateral hypothalamic attachment. RESULTS: EEG-fMRI revealed activation and/or deactivation in subcortical structures and neocortices in all patients. 6/8 patients showed activation in or around the hypothalamus with the HH interface with time-shift model before spike onset. Group analysis showed common activation in the ipsilateral hypothalamus, brainstem tegmentum, and contralateral cerebellum. Deactivation occurred in the default mode network (DMN) and bilateral hippocampi. Among 5 patients with unilateral hypothalamic attachment, activation in or around the ipsilateral hypothalamus was seen in 3 using EEG-fMRI, whereas hyperperfusion was seen in 1 by SISCOM. SIGNIFICANCE: Group analysis of this preliminary study may suggest that the commonly activated subcortical network is related to generation of GS and that frequent spikes lead to deactivation of the DMN and hippocampi, and eventually to a form of epileptic encephalopathy. Inter-individual variance in neocortex activation explains various seizure types among patients. EEG-fMRI enhances sensitivity in detecting the HH interface compared with SISCOM.

Diagnostic utility of FDG-PET in neurolymphomatosis: report of five cases.

Neurolymphomatosis (NL) is a rare condition involving the infiltration of lymphoma cells into the peripheral nervous system. NL can be primary or secondary in the setting of an unknown or known hematologic malignancy, respectively. Here, we report five cases in which F-18 2-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (F-18 FDG-PET/CT) had great value for diagnosing NL. Two cases were rare primary NL, and the other three were secondary NL. Clinical presentations were asymmetric sensorimotor disturbances in the extremities with or without involvement of cranial nerves. Furthermore, all patients experienced spontaneous pain in the face or affected extremities. Cerebrospinal fluid analysis was cytologically negative in two of five cases. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) detected abnormalities in the cranial nerves, nerve roots, and cauda equina in all cases except case 1 and the recurrent stage of case 2. F-18 FDG-PET/CT showed clear visualization of almost all the lymphomatous involvement of peripheral nerves and other tissues in all patients. Furthermore, F-18 FDG-PET/CT detected abnormalities including asymptomatic lesions that were not detected with MRI, and also identified the appropriate lesion for diagnostic biopsy. However, as in case 3, the lesions in the left oculomotor nerve and the cauda equina were detected only with Gd-enhanced MRI, which has superior spatial resolution. In conclusion, F-18 FDG-PET/CT is a sensitive modality that can suggest the presence of malignancy and identify appropriate places for diagnostic biopsies. It is especially useful when combined with Gd-enhanced MRI, even in patients with primary NL that is usually difficult to diagnose.

Intraoperative dorsal language network mapping by using single-pulse electrical stimulation.

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico-cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language-dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High-frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single-pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high-frequency ES of the white matter produced naming impairment, this "eloquent" subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico- and subcortico-cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network.

[Neuroimaging in epilepsy].

It is now recommended that magnetic resonance imaging (MRI) or computed tomography (CT) be carried out in all patients with at least partial- and hopefully also generalized epilepsy to help identify intracranial lesions, such as hippocampal sclerosis, focal cortical dysplasia, brain tumor, cavernous malformation, and arteriovenous malformation. In order to identify epileptic focus, other neuroimaging tools, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetoencephalography (MEG), are also useful, because an epileptogenic area is not necessarily located within these intracranial lesions. With regard to epilepsy surgery, neuroimaging is also required for the identification of functionally essential cortices, such as motor and language areas. MEG and functional MRI are noninvasively, and tractography with diffusion-weighted imaging (DWI) is also useful for visualizing relevant white matter tracts. Recently, it has been reported that the cortico-cortical network plays an important role in preservation of brain function. Thus, cortico-cortical evoked potentials (CCEP) and resting state fMRI are candidate methods to help clarify brain network. While good seizure control is an important treatment outcome for patients with intractable partial epilepsy, the preservation of brain function is equally important. For this reason, further development and clinical application of sophisticated imaging technique are required.

Internal structural changes in the hippocampus observed on 3-tesla MRI in patients with mesial temporal lobe epilepsy.

OBJECTIVE: Hippocampal sclerosis (HS) is observed in many intractable, mesial temporal lobe epilepsy (MTLE) patients. We aimed to delineate the internal structural changes (ISC) shown as loss of internal architecture in the hippocampus on 3-Tesla magnetic resonance imaging (3T-MRI) due to its higher spatial resolution. METHODS: We studied 12 MTLE patients who exhibited unilateral HS on conventional 1.5 Tesla-MRI. Using 3T-MRI, high resolution T2-weighted coronal images of the hippocampus were investigated by visual inspection without the use of detailed clinical information. In addition, tissue samples obtained from four patients who underwent epilepsy surgery were analyzed histopathologically. RESULTS: In addition to hippocampal atrophy (HA) in the abnormal side, blurring of the low-intensity streak, i.e., ISC, in the hippocampus was seen in 12 patients and atrophy or high signal intensity was observed in Ammon's horn or the dentate gyrus in nine patients. After four patients underwent epilepsy surgery, tissue samples showed astrogliosis and a loss of pyramidal neurons in the hippocampal body, concordant with ISC or HA on MRI examination. CONCLUSION: High-resolution MRI suggests that minute internal structural changes in the hippocampus reflect neuronal cell loss or gliosis, possibly in the early stage, and also show laterality of changes more sensitively. Different internal structural changes could further subclassify HS and may predict the surgical outcomes of seizure control based on the clinicopathological correlation.

A novel composite targeting method using high-field magnetic resonance imaging for subthalamic nucleus deep brain stimulation.

OBJECT: Accurate localization of the subthalamic nucleus (STN) is important for proper placement of the electrodes in deep brain stimulation (DBS) surgery for patients with advanced Parkinson disease. The authors evaluated the accuracy of our modified composite targeting method and the value of using high-field MR imaging for targeting the STN. METHODS: Thirteen patients with advanced Parkinson disease underwent bilateral STN DBS based on 3-T MR imaging, and 13 patients underwent surgery based on 1.5-T MR imaging. By sequentially referring to the postmammillary commissure, the red nucleus, the mammillothalamic tract, and the STN, the modified composite targeting method determined the stereotactic coordinates for targeting the STN. The accuracy and efficacy of the composite targeting method and 3-T MR imaging were evaluated by using the intraoperative microelectrode recording, the postoperative imaging study, and the postoperative clinical improvement. RESULTS: The landmark structures for targeting the STN were visualized clearly with 3-T MR imaging. The mean (+/- SD) path length through the STN of the central track was 4.9 +/- 1.1 mm in the 3-T group and 3.1 +/- 2.0 mm in the 1.5-T group (p < 0.001). Twenty-one (81%) of 26 electrodes were placed in the central track in the 3-T group, whereas 8 (31%) of 26 electrodes were placed in the central track in the 1.5-T group (p = 0.006). The rest of the electrodes were placed in the noncentral optimum track for alleviating parkinsonian motor symptoms. The mean Unified Parkinson's Disease Rating Scale motor part score during off period was reduced by 53% in the 3-T group and by 41% in the 1.5-T group (p = 0.14). The mean reductions of levodopa equivalent daily doses were 48.6% in the 3-T group and 43.7% in the 1.5-T group (p = 0.61). CONCLUSIONS: The use of the modified composite targeting method referring to the multiple landmarks with 3-T MR imaging offers reliable and clinically effective target for STN DBS surgery.

Susceptibility-weighted imaging at 3 Tesla delineates the optic radiation.

OBJECTIVES: Some white matter tracts, including the optic radiation (OR), have recently been reported to be delineated as low signal intensity bands (LSBs) on T2*-weighted images at 7 T, presumably because of susceptibility effects caused by myelin.Susceptibility-weighted imaging (SWI) is more sensitive to magnetic susceptibility than T2*-weighted imaging. This study examined whether the LSBs, lateral to the lateral ventricles (LVs) on 3-T SWI, represent the OR. MATERIALS AND METHODS: Subjects comprised 17 healthy volunteers. Transaxial and oblique coronal SWIs orthogonal to the long axes of the inferior horns of the LVs were acquired covering the entire OR at 3 T. For quantification of the LSBs, breadth and thickness of LSBs were measured on planes including: (a) the tip of the inferior horn of the LV, (b) the lateral geniculate body, (c) the trigone of the LV, and (d) the posterior horn of the LV. Distances between the temporal pole and most anterior tip (D) of each LSB were also measured. Diffusion tensor tractography of the OR was also compared with the LSB on SWI in 10 of the 17 subjects. RESULTS: Mean and SD of LSB measurements were breadth: (a) 8.8 +/- 1.8 mm, (b) 18.6 +/- 1.7 mm, (c) 20.5 +/- 3.1 mm, (d) 23.9 +/- 4.1 mm; and thickness: (a) 1.7 +/- 0.4 mm, (b) 2.4 +/- 0.5 mm, (c) 3.7 +/- 0.5 mm, (d) 3.3 +/- 0.4 mm, respectively. Mean D was 32.0 +/- 4.0 mm. These measurements were consistent with the anatomic literature regarding the OR. D on the diffusion tensor tractography was 40.3 +/- 7.7 mm, which was significantly longer than that of the LSB on SWI (31.8 +/- 3.4) for the 10 subjects (P = 0.0002). CONCLUSIONS: SWI at 3 T can constantly delineate the OR. The present study includes novelty in reporting that the entire length of the OR is constantly depicted on SWI, a 3-dimensional high-resolution imaging sequence, at a clinically more widely available 3-T magnetic field.