A 3D Computational Head Model Under Dynamic Head Rotation and Head Extension Validated Using Live Human Brain Data, Including the Falx and the Tentorium.

We employ an advanced 3D computational model of the head with high anatomical fidelity, together with measured tissue properties, to assess the consequences of dynamic loading to the head in two distinct modes: head rotation and head extension. We use a subject-specific computational head model, using the material point method, built from T1 magnetic resonance images, and considering the anisotropic properties of the white matter which can predict strains in the brain under large rotational accelerations. The material model now includes the shear anisotropy of the white matter. We validate the model under head rotation and head extension motions using live human data, and advance a prior version of the model to include biofidelic falx and tentorium. We then examine the consequences of incorporating the falx and tentorium in terms of the predictions from the computational head model.

Rapid, high-resolution, whole-brain, susceptibility-based MRI of multiple sclerosis.

BACKGROUND: Susceptibility-based MRI offers a unique opportunity to study neurological diseases such as multiple sclerosis (MS). In this work, we assessed a three-dimensional segmented echo-planar-imaging (3D-EPI) sequence to rapidly acquire high-resolution T2 -weighted and phase contrast images of the whole brain. We also assessed if these images could depict important features of MS at clinical field strength, and we tested the effect of a gadolinium-based contrast agent (GBCA) on these images. MATERIALS AND METHODS: The 3D-EPI acquisition was performed on four healthy volunteers and 15 MS cases on a 3T scanner. The 3D sagittal images of the whole brain were acquired with a voxel size of 0.55 × 0.55 × 0.55 mm(3) in less than 4 minutes. For the MS cases, the 3D-EPI acquisition was performed before, during, and after intravenous GBCA injection. RESULTS: Both T2-weighted and phase-contrast images from the 3D-EPI acquisition were sensitive to the presence of lesions, parenchymal veins, and tissue iron. Conspicuity of the veins was enhanced when images were obtained during injection of GBCA. CONCLUSIONS: We propose this rapid imaging sequence for investigating, in a clinical setting, the spatiotemporal relationship between small parenchymal veins, iron deposition, and lesions in MS patient brains.

Intracranial arteries in individuals with the elastin gene hemideletion of Williams syndrome.

BACKGROUND AND PURPOSE: Williams syndrome, a rare genetic disorder with a striking neurobehavioral profile characterized by extreme sociability and impaired visuospatial construction abilities, is caused by a hemideletion that includes the elastin gene, resulting in frequent supravavular aortic stenosis and other stenotic arterial lesions. Strokes have been reported in Williams syndrome. Although the extracranial carotid artery has been studied in a sample of patients with Williams syndrome, proximal intracranial arteries have not. MATERIALS AND METHODS: Using MRA, we studied the intracranial vessels in 27 participants: 14 patients with Williams syndrome (age range, 18-44 years; mean age, 27.3 ± 9.1; 43% women) and 13 healthy control participants with similar age and sex distribution (age range, 22-52 years; mean age, 33.4 ± 7.6; 46% women). All participants with Williams syndrome had hemideletions of the elastin gene. Blinded to group allocation or to any other clinical data, a neuroradiologist determined the presence of intracranial vascular changes in the 2 groups. RESULTS: The Williams syndrome group and the healthy control group had similar patency of the proximal intracranial arteries, including the internal carotid and vertebral arteries; basilar artery; and stem and proximal branches of the anterior cerebral artery, MCA, and posterior cerebral arteries. The postcommunicating segment of the anterior cerebral artery was longer in the Williams syndrome group. CONCLUSIONS: Despite the elastin haploinsufficiency, the proximal intracranial arteries in Williams syndrome preserve normal patency.

Segregation of enlarged vestibular aqueducts in families with non-diagnostic SLC26A4 genotypes.

BACKGROUND: Hearing loss with enlarged vestibular aqueduct (EVA) can be inherited as an autosomal recessive trait caused by bi-allelic mutations of SLC26A4. However, many EVA patients have non-diagnostic SLC26A4 genotypes with only one or no detectable mutant alleles. METHODS AND RESULTS: In this study, the authors were unable to detect occult SLC26A4 mutations in EVA patients with non-diagnostic genotypes by custom comparative genomic hybridisation (CGH) microarray analysis or by sequence analysis of conserved non-coding regions. The authors sought to compare the segregation of EVA among 71 families with two (M2), one (M1) or no (M0) detectable mutant alleles of SLC26A4. The segregation ratios of EVA in the M1 and M2 groups were similar, but the segregation ratio for M1 was significantly higher than in the M0 group. Haplotype analyses of SLC26A4-linked STR markers in M0 and M1 families revealed discordant segregation of EVA with these markers in eight of 24 M0 families. CONCLUSION: The results support the hypothesis of a second, undetected SLC26A4 mutation that accounts for EVA in the M1 patients, in contrast to non-genetic factors, complex inheritance, or aetiologic heterogeneity in the M0 group of patients. These results will be helpful for counselling EVA families with non-diagnostic SLC26A4 genotypes.

Gradient echo MRI: implementation of a training tutorial for intracranial hemorrhage diagnosis.

BACKGROUND: Recent studies have demonstrated that gradient echo (GRE) MRI sequences are as accurate as CT for the detection of intracerebral hemorrhage (ICH) in the context of acute stroke. However, many physicians who currently read acute stroke imaging studies may be unfamiliar with interpretation of GRE images. METHODS: An NIH Web-based training program was developed including a pretest, tutorial, and posttest. Physicians involved in the care of acute stroke patients were encouraged to participate. The tutorial covered acute, chronic, and mimic hemorrhages as they appear on CT, diffusion-weighted imaging, and GRE sequences. Ability of users to identify ICH presence, type, and age on GRE was compared from the pretest to posttest timepoint. RESULTS: A total of 104 users completed the tutorial. Specialties represented included general radiology (42%), general neurology (16%), neuroradiology (15%), stroke neurology (14%), emergency medicine (1%), and other (12%). Median overall score improved pretest to posttest from 66.7% to 83.3%, p < 0.001. Improvement by category was as follows: acute ICH, 66.7%-100%, p < 0.001; chronic ICH, 33.3%-66.7%, p < 0.001; ICH negatives/mimics, 100%-100%, p = 0.787. Sensitivity for identification of acute hemorrhage improved from 68.2% to 96.4%. CONCLUSIONS: Physicians involved in acute stroke care achieved significant improvement in gradient echo (GRE) hemorrhage interpretation after completing the NIH GRE MRI tutorial. This indicates that a Web-based tutorial may be a viable option for the widespread education of physicians to achieve an acceptable level of diagnostic accuracy at reading GRE MRI, thus enabling confident acute stroke treatment decisions.

Altered language processing in autosomal dominant partial epilepsy with auditory features.

BACKGROUND: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is an idiopathic focal epilepsy syndrome with auditory symptoms or receptive aphasia as major ictal manifestations, frequently associated with mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene. Although affected subjects do not have structural abnormalities detected on routine MRI, a lateral temporal malformation was identified through high resolution MRI in one family. We attempted to replicate this finding and to assess auditory and language processing in ADPEAF using fMRI and magnetoencephalography (MEG). METHODS: We studied 17 subjects (10 affected mutation carriers, 3 unaffected carriers, 4 noncarriers) in 7 ADPEAF families, each of which had a different LGI1 mutation. Subjects underwent high-resolution structural MRI, fMRI with an auditory description decision task (ADDT) and a tone discrimination task, and MEG. A control group comprising 26 volunteers was also included. RESULTS: We found no evidence of structural abnormalities in any of the 17 subjects. On fMRI with ADDT, subjects with epilepsy had significantly less activation than controls. On MEG with auditory stimuli, peak 2 auditory evoked field latency was significantly delayed in affected individuals compared to controls. CONCLUSIONS: These findings do not support the previous report of a lateral temporal malformation in autosomal dominant partial epilepsy with auditory features (ADPEAF). However, our fMRI and magnetoencephalography data suggest that individuals with ADPEAF have functional impairment in language processing.

Decreased thickness of primary motor cortex in primary lateral sclerosis.

BACKGROUND AND PURPOSE: Primary lateral sclerosis (PLS) is a rare form of motor neuron disease characterized by upper motor neuron dysfunction. Because pathologic examination has revealed a loss of neurons in the motor cortex of patients with PLS, we sought to confirm and extend this finding by using MR imaging to measure cortical thickness. METHODS: Seven patients with PLS and 7 age-matched neurologically normal control subjects were examined with heavily T1-weighted short-tau inversion recovery (STIR) MR imaging performed at 3T. Cortical thickness in the anterior and posterior banks of both the central and precentral sulci were measured. RESULTS: Primary motor cortex (M1) was significantly thinner in patients with PLS than M1 in healthy control subjects, measuring 2.32 +/- 0.21 mm compared with 2.79 +/- 0.18 mm (P = .0008). Cortical thickness did not differ between the 2 groups for primary sensory cortex or for the anterior or posterior banks of the precentral sulcus. Therefore, loss of gray matter was specific to motor cortex. Although this difference was modest, cortical thickness discriminated between the 2 groups; only 1 PLS case was within the range of normal measurements. CONCLUSION: Decreased thickness of M1 on the anterior bank of the precentral sulcus in patients with PLS, demonstrable by MR imaging, indicates a selective loss of upper motor neurons in this disease. Measurements of cortical thickness by MR imaging may provide a useful biomarker for diagnosis and study of upper motor neuron diseases.

Image-guided, direct convective delivery of glucocerebrosidase for neuronopathic Gaucher disease.

OBJECTIVE: To determine if convection-enhanced delivery (CED) of glucocerebrosidase could be used to treat targeted sites of disease progression in the brain and brainstem of a patient with neuronopathic Gaucher disease while monitoring enzyme distribution using MRI. METHODS: A CED paradigm in rodents (n = 8) and primates (n = 5) that employs co-infusion of a surrogate MRI tracer (gadolinium diethylenetriamine penta-acetic acid [Gd-DTPA]) with glucocerebrosidase to permit real-time monitoring of distribution was developed. The safety and feasibility of this delivery and monitoring paradigm were evaluated in a patient with type 2 Gaucher disease. RESULTS: Animal studies revealed that real-time, T1-weighted, MRI of Gd-DTPA accurately tracked enzyme distribution during CED. Targeted perfusion of clinically affected anatomic sites in a patient with neuronopathic Gaucher disease (frontal lobe and brainstem) with glucocerebrosidase was successfully performed. Real-time MRI revealed progressive and complete filling of the targeted region with enzyme and Gd-DTPA infusate. The patient tolerated the infusions without evidence of toxicity. CONCLUSIONS: Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Co-infused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with neuronopathic Gaucher disease and other intrinsic CNS disorders may benefit from a similar treatment paradigm.

In vivo detection of cortical plaques by MR imaging in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: In vivo detection of cortical lesions in patients with multiple sclerosis (MS) by MR imaging is hampered by several factors. Among them is the low contrast between small cortical lesions and surrounding cortical gray matter offered by present techniques. METHODS: T1-weighted 3D spoiled gradient-recalled-echo (SPGR) volumes and 2D fluid-attenuated inversion recovery (FLAIR) sequences of 22 patients with MS who had 12 monthly brain MR imaging examinations at 1.5T, using a quadrature head coil, were retrospectively analyzed. These serial studies were coregistered and averaged to generate a single high signal-to-noise ratio (SNR) mean image, which was used to identify cortical lesions. The means of 12 FLAIRs and SPGRs from 14 age- and sex-matched healthy volunteers were analyzed as well. RESULTS: No cortical lesions were found on images of healthy subjects. Eighty-six cortical lesions were identified in 13 (59.1%) patients, predominantly in the frontal lobe (73.3%); 23.3% of cortical lesions lay entirely in the cortex, whereas the remaining lesions invaded the white matter underneath. CONCLUSION: Averaging multiple SPGRs created a single high SNR volume, allowing identification of cortical lesions. Because data were obtained monthly for 1 year, the average image does not account for transient lesion activity. However, for cortical lesions that remained stable during this time, the findings are valid in demonstrating the importance of high SNR images for detecting cortical brain abnormalities in MS.

Treatment of neurocysticercosis: current status and future research needs.

Here we put forward a roadmap that summarizes important questions that need to be answered to determine more effective and safer treatments. A key concept in management of neurocysticercosis is the understanding that infection and disease due to neurocysticercosis are variable and thus different clinical approaches and treatments are required. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experience. A better understanding of basic pathophysiologic mechanisms including parasite survival and evolution, nature of the inflammatory response, and the genesis of seizures, epilepsy, and mechanisms of anthelmintic action should lead to improved therapies.

Differential cortical thickness across the central sulcus: a method for identifying the central sulcus in the presence of mass effect and vasogenic edema.

BACKGROUND AND PURPOSE: Identification of the motor strip on MR imaging studies is difficult in the presence of mass effect and vasogenic edema because sulcal landmarks are obscured. We hypothesize that a difference in cortical thickness between the motor and sensory strips is readily apparent on T2-weighted images in the presence of vasogenic edema and reliably identifies the central sulcus. METHODS: Thirteen patients with brain tumors resulting in vasogenic edema near the central sulcus were identified. The cortical thickness of the anterior and posterior banks of the central sulcus as well as the neighboring sulci in the frontal and parietal lobes were measured from T2-weighted images. Similar measures were obtained from neighboring sulci in the frontal and parietal lobes. Location of the central sulcus was confirmed with standard anatomic landmarks in all patients and by intraoperative cortical mapping in 2 patients. RESULTS: A twofold difference in cortical thickness between the anterior and posterior banks of the central sulcus uniquely identified the central sulcus on T2-weighted images in the presence of vasogenic edema, despite the marked distortion of sulcal anatomy as a result of mass effect. This relationship was not present in neighboring sulci. CONCLUSION: Cytoarchitectonic differences in the motor and sensory cortices result in a markedly thicker posterior than anterior bank of the central sulcus that is readily visible on routine T2-weighted images in the presence of vasogenic edema. Therefore, the cortical thickness can serve as a complementary method in identification of the motor strip in patients with mass effect.

Calcific neurocysticercosis and epileptogenesis.

Neurocysticercosis is responsible for increased rates of seizures and epilepsy in endemic regions. The most common form of the disease, chronic calcific neurocysticercosis, is the end result of the host's inflammatory response to the larval cysticercus of Taenia solium. There is increasing evidence indicating that calcific cysticercosis is not clinically inactive but a cause of seizures or focal symptoms in this population. Perilesional edema is at times also present around implicated calcified foci. A better understanding of the natural history, frequency, epidemiology, and pathophysiology of calcific cysticercosis and associated disease manifestations is needed to define its importance, treatment, and prevention.

Primary lateral sclerosis: A heterogeneous disorder composed of different subtypes?

OBJECTIVE: To determine identifiable subgroups of patients with primary lateral sclerosis (PLS) with distinct clinical features as a first step in identifying patients likely to have the same disorder. METHODS: Twenty-five patients meeting previously proposed diagnostic criteria for PLS were seen for examination, measurement of gait and finger tapping speed, and physiologic tests to assess motor pathways. Motor cortex excitability and central motor conduction time were assessed with transcranial magnetic stimulation. Brainstem motor pathways were assessed by the acoustic startle reflex. MRS was performed in a subgroup of patients to assess metabolites in the motor cortex. RESULTS: Fifty-six percent of the patients with PLS had a similar pattern of symptom progression, which the authors termed ascending. In these patients spasticity began in the legs and progressed slowly and steadily. Spasticity in the arms developed 3.6 years after the legs, on average, and speech impairment followed 1.5 years later. Motor evoked potentials were absent. MRS showed a mean reduction of N-acetylaspartate/creatinine in the motor cortex. The remaining patients with PLS had heterogeneous patterns of symptom progression and physiology. CONCLUSIONS: Patients with PLS with an ascending progression of symptoms form a distinct clinical subgroup that may be amenable to investigations of etiology and treatment.

Overview of imaging in multiple sclerosis and white matter disease.

MR imaging is the dominant paraclinical test for evaluating multiple sclerosis (MS) because of its exquisite sensitivity to white matter pathology. Knowledge of the signal characteristics of MS lesions, anatomic distribution of lesions, differential diagnosis, and most important, the clinical context, markedly improve the specificity of the MR examination. MR imaging findings can be used to predict future conversion to clinically definite MS before a second clinical exacerbation.

Combination-sensitive neurons in the primary auditory cortex of the mustached bat.

In the mustached bat, Pteronotus parnellii, neurons in the primary auditory cortex (AI) have been thought to respond primarily to single frequencies, as in other mammals. However, neurons in the Doppler-shifted constant-frequency (DSCF) area, a part of the mustached bat's AI that contains an overrepresentation of the prominent CF2 component of the biosonar signal, were found to show facilitative responses to combinations of different frequencies in the pulse and echo. The essential components for facilitation were the pulse FM1 and the echo CF2. The FM1-CF2 facilitation was sensitive to echo delays, indicating that DSCF neurons respond better to targets within particular ranges. On average, the longest discriminable echo delay, based on increased impulse counts due to facilitation, corresponded to a target range of 4.3 m, and the most discriminable delay corresponded to a target 3.6 m distant. Since mustached bats first show a behavioral response to a target at a distance of 3-4 m, DSCF neurons are suited to signal the presence of an insect within this behaviorally important range. DSCF neurons were broadly tuned to echo delay, with the average minimum discriminable echo delay corresponding to a target range of 1.9 m, and the delay tuning of the neurons followed (tracked) changes in pulse duration, indicating that facilitation occurs during much of the approach phase of insect pursuit when target characterization is presumably occurring. These results show that AI neurons in the mustached bat are specialized to respond to complex, behaviorally relevant stimuli during the search and approach phases of insect pursuit.