Image-derived Metrics Quantifying Hemodynamic Instability Predicted Growth of Unruptured Intracranial Aneurysms.

Background: While image-derived predictors of intracranial aneurysm (IA) rupture have been well-explored, current understanding of IA growth is limited. Pulsatility index (PI) and wall shear stress pulsatility index (WSSPI) are important metrics measuring temporal hemodynamic instability. However, they have not been investigated in IA growth research. The present study seeks to verify reliable predictors of IA growth with comparative analyses of several important morphological and hemodynamic metrics between stable and growing cases among a group of unruptured IAs. Methods: Using 3D images, vascular models of 16 stable and 20 growing cases were constructed and verified using Geodesic techniques. With an overall mean follow-up period of 25 months, cases exhibiting a 10% or higher increase in diameter were considered growing. Patient-specific, pulsatile simulations were performed, and hemodynamic calculations were computed at 5 important regions of each aneurysm (inflow artery, aneurysm neck, body, dome, and outflow artery). Index values were compared between growing and stable IAs using ANCOVA controlling for aneurysm diameter. Stepwise multiple logistic regression and ROC analyses were conducted to investigate predictive models of IA growth. Results: Compared to stable IAs, growing IAs exhibited significantly higher intrasaccular PI, intrasaccular WSSPI, intrasaccular spatial flow rate deviation, and intrasaccular spatial wall shear stress (WSS) deviation. Stepwise logistic regression analysis revealed a significant predictive model involving PI at aneurysm body, WSSPI at inflow artery, and WSSPI at aneurysm body. Conclusions: Our results showed that high degree of hemodynamic variations within IAs is linked to growth, even after controlling for morphological parameters. Further, evaluation of PI in conjunction with WSSPI yielded a highly accurate predictive model of IA growth. Upon validation in future cohorts, these metrics may aid in early identification of IA growth and current understanding of IA remodeling mechanism.

MR Angiography in Assessment of Collaterals in Patients with Acute Ischemic Stroke: A Comparative Analysis with Digital Subtraction Angiography.

Collateral status has prognostic and treatment implications in acute ischemic stroke (AIS) patients. Unlike CTA, grading collaterals on MRA is not well studied. We aimed to evaluate the accuracy of assessing collaterals on pretreatment MRA in AIS patients against DSA. AIS patients with anterior circulation proximal arterial occlusion with baseline MRA and subsequent endovascular treatment were included. MRA collaterals were evaluated by two neuroradiologists independently using the Tan and Maas scoring systems. DSA collaterals were evaluated by using the American Society of Interventional and Therapeutic Neuroradiology grading system and were used as the reference for comparative analysis against MRA. A total of 104 patients met the inclusion criteria (59 female, age (mean ± SD): 70.8 ± 18.1). The inter-rater agreement (k) for collateral scoring was 0.49, 95% CI 0.37-0.61 for the Tan score and 0.44, 95% CI 0.26-0.62 for the Maas score. Total number (%) of sufficient vs. insufficient collaterals based on DSA was 49 (47%) and 55 (53%) respectively. Using the Tan score, 45% of patients with sufficient collaterals and 64% with insufficient collaterals were correctly identified in comparison to DSA, resulting in a poor agreement (0.09, 95% CI 0.1-0.28). Using the Maas score, only 4% of patients with sufficient collaterals and 93% with insufficient collaterals were correctly identified against DSA, resulting in poor agreement (0.03, 95% CI 0.06-0.13). Pretreatment MRA in AIS patients has limited concordance with DSA when grading collaterals using the Tan and Maas scoring systems.

Beyond the Golden Hour: Treating Acute Stroke in the Platinum 30 Minutes.

BACKGROUND: To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized. METHODS: In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy-Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients. RESULTS: Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25-30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57-79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3-5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3-18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0-1) in 35.5%, functional independence (modified Rankin Scale score, 0-2) in 53.2%, and mortality in 17.7%. CONCLUSIONS: Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.

National Institutes of Health Stroke Scale Correlates Well with Initial Intracerebral Hemorrhage Volume.

OBJECTIVES: The US Centers for Medicare and Medicaid Services (CMS) currently publicly reports hospital-quality, risk-adjusted mortality measure for ischemic stroke but not intracerebral hemorrhage (ICH). The NIHSS, which is captured in CMS administrative claims data, is a candidate metric for use in ICH risk adjustment and has been shown to predict clinical outcome with accuracy similar to the ICH Score. Correlation between early NIHSS and initial ICH volume would further support use of the NIHSS for ICH risk adjustment. MATERIALS AND METHODS: Among 372 ICH patients enrolled in a large multicenter trial (FAST-MAG), the relation between early NIHSS and early ICH volume was assessed with correlation and linear trend analysis. RESULTS: Overall, there was strong correlation between NIHSS and ICH volume, r = 0.77 (p < 0.001), and for every 10cc increase in ICH the NIHSS increased by 4.5 points. Correlation coefficients were comparable in all subgroups, but magnitude of NIHSS increase with ICH unit volume increase was greater with left than right hemispheric ICH, with presence rather than absence of IVH, with imaging done within the first hour than second hour after last known well, with men than women, and with younger than older patients. CONCLUSION: Early NIHSS neurologic deficit severity values correlate strongly with initial ICH hematoma volume. As with ischemic stroke, lesion volume increases produce greater NIHSS change in the left than right hemisphere, reflecting greater NIHSS sensitivity to left hemisphere function. These findings provide further support for the use of NIHSS in risk-adjusted mortality measures for intracerebral hemorrhage.

Trans-synaptic degeneration of the optic radiation from optic nerve atrophy.

Fourty-seven-year-old woman with 5-year history of progressive decreased left eye vision. Optical coherence tomography showed optic nerve atrophy (left > right) and brain MRI revealed T2 hyperintense signal along the course of left optic radiations. We present a case of a trans-synaptic degeneration of the optic radiation in a patient with confirmed optic atrophy. Trans-synaptic degeneration of the optic radiation without associated infarct or inflammatory disease has not been reported before in patients with optic atrophy.

Evaluation of a Workflow to Define Low Specific Absorption Rate MRI Protocols for Patients With Active Implantable Medical Devices.

BACKGROUND: MRI exams for patients with MR-conditional active implantable medical devices (AIMDs) are contraindicated unless specific conditions are met. This limits the maximum specific absorption rate (SAR, W/kg). Currently, there is no general framework to guide meeting a lower SAR limit. PURPOSE: To design and evaluate a workflow for modifying MRI protocols to whole-body SAR (WB-SAR ≤0.1 W/kg) and local-head SAR (LH-SAR ≤0.3 W/kg) limits while mitigating the impact on image quality and exam time. STUDY TYPE: Prospective. POPULATION: Twenty healthy volunteers on head (n = 5), C-spine (n = 5), T-spine (n = 5), and L-spine (n = 5) with IRB consent. ASSESSMENT: Vendor-provided head, C-spine, T-spine, and L-spine protocols (SARRT ) were modified to meet both low SAR targets (SARLOW ) using the proposed workflow. in vitro SNR and CNR were evaluated with a T1 -T2 phantom. in vivo image quality and clinical acceptability were scored using a 5-point Likert scale for two blinded readers. FIELD STRENGTH/SEQUENCES: 1.5T/spin-echoes, gradient-echoes. STATISTICAL ANALYSIS: In vitro SNR and CNR values were evaluated with a repeated measures general linear model. in vivo image quality and clinical acceptability were evaluated using a generalized estimating equation analysis (GEE). The two reader's level of agreement was analyzed using Cohen's kappa statistical analysis. RESULTS: Using the workflow, SAR limits were met. LH-SAR: 0.12 ± 0.02 W/kg, median (SD) values for LH-SAR were 0.12 (0.02) W/kg and WB-SAR: 0.09 (0.01) W/kg. Examination time did not increase ≤2x the initial time. SARRT SNR values were higher and significantly different than SARLOW (P < 0.05). However, no significant difference was observed between the CNR values (value = 0.21). Median (IQR) CNR values were 14.2 (25.0) vs. 15.1 (9.2) for head, 12.1 (16.9) vs. 25.3 (14.2) for C-spine, 81.6 (70.1) vs. 71.0 (26.6) for T-spine, and 51.4 (52.6) vs. 37.7 (27.3) for L-spine. Image quality scores were not significantly different between SARRT and SARLOW (median [SD] scores were 4.0 [0.01] vs. 4.3 [0.2], P > 0.05). DATA CONCLUSION: The proposed workflow provides guidance for modifying routine MRI exams to achieve low SAR limits. This can benefit patients referred for an MRI exam with low SAR MR-conditional AIMDs. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;52:91-102.

Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study.

OBJECTIVE: Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE. METHODS: We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury. RESULTS: Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p < 0.001), worse functional recovery (p = 0.003), and greater temporal lobe atrophy (p = 0.029). CONCLUSION: Our results indicate that in a cohort of patients with a moderate-severe TBI, 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of PTE, 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.

Six-minute magnetic resonance imaging protocol for evaluation of acute ischemic stroke: pushing the boundaries.

BACKGROUND AND PURPOSE: If magnetic resonance imaging (MRI) is to compete with computed tomography for evaluation of patients with acute ischemic stroke, there is a need for further improvements in acquisition speed. METHODS: Inclusion criteria for this prospective, single institutional study were symptoms of acute ischemic stroke within 24 hours onset, National Institutes of Health Stroke Scale ≥3, and absence of MRI contraindications. A combination of echo-planar imaging (EPI) and a parallel acquisition technique were used on a 3T magnetic resonance (MR) scanner to accelerate the acquisition time. Image analysis was performed independently by 2 neuroradiologists. RESULTS: A total of 62 patients met inclusion criteria. A repeat MRI scan was performed in 22 patients resulting in a total of 84 MRIs available for analysis. Diagnostic image quality was achieved in 100% of diffusion-weighted imaging, 100% EPI-fluid attenuation inversion recovery imaging, 98% EPI-gradient recalled echo, 90% neck MR angiography and 96% of brain MR angiography, and 94% of dynamic susceptibility contrast perfusion scans with interobserver agreements (k) ranging from 0.64 to 0.84. Fifty-nine patients (95%) had acute infarction. There was good interobserver agreement for EPI-fluid attenuation inversion recovery imaging findings (k=0.78; 95% confidence interval, 0.66-0.87) and for detection of mismatch classification using dynamic susceptibility contrast-Tmax (k=0.92; 95% confidence interval, 0.87-0.94). Thirteen acute intracranial hemorrhages were detected on EPI-gradient recalled echo by both observers. A total of 68 and 72 segmental arterial stenoses were detected on contrast-enhanced MR angiography of the neck and brain with k=0.93, 95% confidence interval, 0.84 to 0.96 and 0.87, 95% confidence interval, 0.80 to 0.90, respectively. CONCLUSIONS: A 6-minute multimodal MR protocol with good diagnostic quality is feasible for the evaluation of patients with acute ischemic stroke and can result in significant reduction in scan time rivaling that of the multimodal computed tomographic protocol.

Clinical functional anatomy of the pterygopalatine ganglion, cephalgia and related dysautonomias: A review.

The purpose of this article is to explain the anatomy of the pterygopalatine ganglion (PPG), its location in the pterygopalatine fossa (PPF) in the skull, and the relationship it has to the Vidian nerve terminal branches and the fifth cranial nerve. An overview of the neuro-anatomical/clinical correlations, a spectrum of pathologies affecting the seventh cranial nerve and some therapies both medical and surgical are noted. The focus is the pterygopalatine region with discussion of the proximal courses of the seventh and fifth cranial nerves and their pathological processes. The ganglion is used as an example of neuro-anatomical model for explaining cluster headaches (CH). Radiological correlation is included to clarify the location of the PPF and its clinical importance.

An infundibulum of thalamoperforator arteries: Importance of angiographic images for appropriate diagnosis.

BACKGROUND: The identification of infundibula on noninvasive imaging modalities may be challenging. Because these lesions have generally been viewed as nonpathological, distinguishing them from small or micro-aneurysms is important. CASE DESCRIPTION: A 39-year-old male was diagnosed with recurrence of typical orgasmic headache. An outpoutching arising from the distal part of the right P1 at the take-off of thalamoperforator arteries was visualized on noninvasive investigations. The patient was referred to neurosurgery for surgical management of a right P1 aneurysm. Its unusual location and morphology led to be suspicious of an infundibular dilatation. Catheter angiography with 2D projections and 3D rotational reconstruction revealed an infundibulum at the common origin of two thalamoperforators, giving rise to a double-peaked shape, mimicking a true aneurysm, rather than the more characteristic conical shape of an infundibulum. CONCLUSION: Although noninvasive modalities may identify typical infundibula, the catheter angiogram with 2D projections was critical to establishing the diagnosis. The 3D rotational reconstruction enabled a straightforward understanding of the 3D vascular anatomy. This pyramidal variant of infundibular dilatation should be included in the differential diagnosis of a wide-based nonsaccular arterial contour deformities located in an area of multiple perforators.

Enlargement of small, asymptomatic, unruptured intracranial aneurysms in patients with no history of subarachnoid hemorrhage: the different factors related to the growth of single and multiple aneurysms.

OBJECT: This study was performed to investigate the risk factors related to the growth of small, asymptomatic, unruptured aneurysms in patients with no history of subarachnoid hemorrhage (SAH). METHODS: Between January 2005 and December 2010, a total of 508 patients in whom unruptured intracranial aneurysms were diagnosed at the University of California, Los Angeles medical center did not receive treatment to prevent rupture. Of these, 235 patients with no history of SAH who had asymptomatic, small, unruptured aneurysms (<7 mm) were monitored with 3D CT angiography images. Follow-up images of the lesions were used to measure aneurysm size changes. Patient medical history, family history of SAH, aneurysm size, and location were studied to find the risk factors associated with small aneurysm growth. RESULTS: A total of 319 small aneurysms were included, with follow-up durations of 29.2±20.6 months. Forty-two aneurysms increased in size during the follow-up; 5 aneurysms grew to become ≥7 mm within 38.2±18.3 months. A trend of higher growth rates was found in single aneurysms than in multiple aneurysms (p=0.07). A history of stroke was the only factor associated with single aneurysm growth (p=0.03). The number of aneurysms (p=0.011), number of aneurysms located within the posterior circulation (p=0.030), and patient history of transient ischemic attack (p=0.044) were related to multiple aneurysm growth. CONCLUSIONS: Multiple small aneurysms are more likely to grow, and multiple aneurysms located in the posterior circulation may require additional attention. Although single aneurysms have a lower risk of growth, a trend of higher growth rates in single aneurysms was found.

Multimodal magnetic resonance imaging assessment of white matter aging trajectories over the lifespan of healthy individuals.

BACKGROUND: Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers. METHODS: Healthy subjects (n = 171) 14-93 years of age were examined with transverse relaxation rate (R(2)) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively). RESULTS: Only R(2) reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R(2) < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R(2) and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor. CONCLUSIONS: The R(2) and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.

Thrombus branching and vessel curvature are important determinants of middle cerebral artery trunk recanalization with Merci thrombectomy devices.

BACKGROUND AND PURPOSE: Determinants of successful recanalization likely differ for Merci thrombectomy and intra-arterial pharmacological fibrinolysis interventions. Although the amount of thrombotic material to be digested is an important consideration for chemical lysis, mechanical debulking may be more greatly influenced by other target lesion characteristics. METHODS: In consecutive patients with acute ischemic stroke treated with Merci thrombectomy for middle cerebral artery M1 occlusions, we analyzed the influence on recanalization success and clinical outcome of target thrombus size (length) and shape (curvature and branching) on pretreatment T2* gradient echo MRI. RESULTS: Among 65 patients, pretreatment MRI showed susceptibility vessel signs in 45 (69%). Thrombus length averaged 13.03 mm (range, 5.56-34.91) and irregular shape (curvature or branching) was present in 17 of 45 (38%). Presence and length of susceptibility vessel signs did not predict recanalization or good clinical outcome. Substantial recanalization (Thrombolysis In Cerebral Infarction 2b or 3) and good clinical outcome (modified Rankin Scale score ≤2) were more frequent with regular than irregular susceptibility vessel signs shape (57% versus 18%, P=0.013; 39% versus 6%, P=0.017). On multiple regression analysis, the only independent predictor of substantial recanalization was irregular susceptibility vessel signs (OR, 0.16; 95% CI, 0.04-0.69; P=0.014); and leading predictors of good clinical outcome were baseline National Institutes of Health Stroke Scale (OR, 1.20; 95% CI, 1.03-1.40; P= 0.019) and irregular susceptibility vessel signs (OR, 9.36; 95% CI, 0.98-89.4; P=0.052). CONCLUSIONS: Extension of thrombus into middle cerebral artery division branches and curving shape of the middle cerebral artery stem, but not thrombus length, decrease technical and clinical success of Merci thrombectomy in M1 occlusions.

Gender and iron genes may modify associations between brain iron and memory in healthy aging.

Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON+) vs noncarrier (IRON-) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON+ vs IRON- status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r=-0.50, p=0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRON- group (r=-0.49, p=0.005) but not in the IRON+ group. Between-group interactions (p=0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men.

Prevalent gene variants involved in iron metabolism [hemochromatosis (HFE) H63D and transferrin C2 (TfC2)] have been associated with higher risk and earlier age at onset of Alzheimer's disease (AD), especially in men. Brain iron increases with age, is higher in men, and is abnormally elevated in several neurodegenerative diseases, including AD and Parkinson's disease, where it has been reported to contribute to younger age at onset in men. The effects of the common genetic variants (HFE H63D and/or TfC2) on brain iron were studied across eight brain regions (caudate, putamen, globus pallidus, thalamus, hippocampus, white matter of frontal lobe, genu, and splenium of corpus callosum) in 66 healthy adults (35 men, 31 women) aged 55 to 76. The iron content of ferritin molecules (ferritin iron) in the brain was measured with MRI utilizing the Field Dependent Relaxation Rate Increase (FDRI) method. 47% of the sample carried neither genetic variant (IRON-) and 53% carried one and/or the other (IRON+). IRON+ men had significantly higher FDRI compared to IRON- men (p=0.013). This genotype effect was not observed in women who, as expected, had lower FDRI than men. This is the first published evidence that these highly prevalent genetic variants in iron metabolism genes can influence brain iron levels in men. Clinical phenomena such as differential gender-associated risks of developing neurodegenerative diseases and age at onset may be associated with interactions between iron genes and brain iron accumulation. Clarifying mechanisms of brain iron accumulation may help identify novel interventions for age-related neurodegenerative diseases.

Lifespan trajectory of myelin integrity and maximum motor speed.

OBJECTIVE: Myelination of the human brain results in roughly quadratic trajectories of myelin content and integrity, reaching a maximum in mid-life and then declining in older age. This trajectory is most evident in vulnerable later myelinating association regions such as frontal lobes and may be the biological substrate for similar trajectories of cognitive processing speed. Speed of movement, such as maximal finger tapping speed (FTS), requires high-frequency action potential (AP) bursts and is associated with myelin integrity. We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity. METHODS: A sensitive in vivo MRI biomarker of myelin integrity (calculated transverse relaxation rates (R(2))) of frontal lobe white matter (FLwm) was measured in a sample of very healthy males (N=72) between 23 and 80 years of age. To assess specificity, R(2) of a contrasting early-myelinating region (splenium of the corpus callosum) was also measured. RESULTS: FLwm R(2) and FTS measures were significantly correlated (r=.45, p<.0001) with no association noted in the early-myelinating region (splenium). Both FLwm R(2) and FTS had significantly quadratic lifespan trajectories that were virtually indistinguishable and both reached a peak at 39 years of age and declined with an accelerating trajectory thereafter. CONCLUSIONS: The results suggest that in this very healthy male sample, maximum motor speed requiring high-frequency AP burst may depend on brain myelin integrity. To the extent that the FLwm changes assessed by R(2) contribute to an age-related reduction in AP burst frequency, it is possible that other brain functions dependent on AP bursts may also be affected. Non-invasive measures of myelin integrity together with testing of basic measures of processing speed may aid in developing and targeting anti-aging treatments to mitigate age-related functional declines.

Carotid computed tomography angiography with automated bone suppression: a comparative study between dual energy and bone subtraction techniques.

OBJECTIVES: Computed tomography angiography (CTA) is a well-accepted imaging modality to evaluate the vessels of the head and neck. To improve the assessment of vessels at or within the skull base, different techniques to suppress bone in the final CTA image have been developed. We sought to compare the performance of fully automated bone removal based on dual energy (DE) and image registration (bone subtraction CTA [BSCTA]) for the supraaortic vasculature. MATERIALS AND METHODS: Twenty-seven patients underwent carotid CTA on a dual source CT system. Two scans were performed, one before and one after contrast agent injection in DE mode (simultaneous acquisition of 80 and 140 kV scans). For each patient, data sets were reconstructed for post processing with DE and BSCTA. Two examiners evaluated overall bone suppression and image quality regarding integrity of the vessel lumen of different vessel segments (n = 19) with a 5-point scale (1 = poor, 5 = excellent), CTA source data served as the reference. Wilcoxon signed rank test was used to determine differences between the techniques. Cohen's kappa was used to determine interobserver agreement. RESULTS: Both bone suppression techniques could be applied successfully in 25 patients with high overall image quality. Two patients were excluded from the evaluation for technical reasons. Interobserver agreement was excellent (kappa = 0.85). Mean score of all vessel segments for overall bone removal was 4.45 +/- 0.76 for DE and 4.33 +/- 1.02 for BSCTA; DE performed better in the vessel segment of the neck (external carotid artery, common carotid artery, V1 to V3 segment of the vertebral artery, subclavian artery), whereas BSCTA was superior in the cranial vessels (C3-C6 segment of the internal carotid artery, ophthalmic artery). Vessel integrity was superior with BSCTA, the mean score of all vessel segments for overall vessel integrity was 3.97 +/- 1.47 for DE and 4.49 +/- 0.98 for BSCTA, the subclavian artery was most frequently truncated using DE post processing (mean score: 1.44 +/- 1.2). CONCLUSIONS: Both techniques provided bone suppression in a fully automated way. DE provided more complete bone suppression in the neck, but at the cost of inferior vessel integrity, especially at the thoracic inlet. BSCTA showed excellent results for vessel integrity and was superior to DE in most of the vessels in or at the skull base.

Cranial computed tomography angiography with automated bone subtraction: a feasibility study.

OBJECTIVES: Computed tomography angiography (CTA) is becoming an increasingly accepted noninvasive alternative to catheter angiography. To display continuous vessel contours without superimposed bone in a similar manner, postprocessing of the CTA data is necessary. Threshold-based techniques often fail in regions of close vessel-bone contact, which frequently requires user interaction to optimize the results. This may be laborious and time consuming. The aim of this study was to assess the feasibility of a fully automated algorithm for bone subtraction in cranial CT angiography. MATERIALS AND METHODS: Forty-nine patients underwent cranial CT angiography on 64 slice CT systems. Two scans were performed, one before (mask) and one after (CTA) contrast agent administration. Images were processed with commercially available subtraction software. Two examiners rated the success of overall bone removal and image quality of different vessel segments (n = 34) with a 4-point scale (1 = poor; 4 = excellent); original CTA data served as the reference. RESULTS: Subtraction was performed successfully in all cases, overall subtraction quality was high (82% of cases were rated good or excellent). Only 50 of 1666 arterial segments (3%) were rated nondiagnostic. No relevant artificial stenoses of the internal carotid artery (ICA) or vertebral artery along their way through the skull base were detected when comparing CTA source images to bone subtraction computed tomography angiography (BSCTA) images. CONCLUSIONS: Automatic subtraction provides diagnostic image quality for 3D visualization of intracranial vessels, free from over projecting bone in a fully automatic way. Aneurysms can be evaluated from all angles, and ICA stenoses at the skull base were easily visualized.

Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury.

OBJECTIVE: To determine whether persistent metabolic dysfunction in normal-appearing frontal lobe tissue is correlated with long-term tissue atrophy. DESIGN: Prospective monitoring with retrospective data analysis. SETTING: Single-center academic neurointensive care unit. PATIENTS: Fifteen patients with moderate to severe traumatic brain injury (Glasgow Coma Scale score 3-12). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hourly cerebral microdialysis was performed for the initial 96 hrs after trauma to determine extracellular levels of glucose, glutamate, glycerol, lactate, and pyruvate in normal appearing frontal lobes. Six months after injury, the anatomical outcome was assessed by measures of global and regional cerebral atrophy using volumetric brain magnetic resonance imaging. The lactate/pyruvate ratio was elevated >40 after traumatic brain injury in most patients, with a mean percent time of 32 +/- 29% of hours monitored. At 6 months after traumatic brain injury, there was a mean frontal lobe atrophy of 12 +/- 11% and global brain atrophy of 8.5 +/- 4.5%. The percentage of time of elevated lactate/pyruvate ratio correlated with the extent of frontal lobe brain atrophy (r = -.56, p < 0.01), but not global brain atrophy (r = -.31, p = 0.20). The predictive effect of lactate/pyruvate ratio was independent of patient age, Glasgow Coma Scale score, and volume of frontal lobe contusion. CONCLUSION: Persistent metabolic crisis, as reflected by an elevated lactate/pyruvate ratio, in normal appearing posttraumatic frontal lobe, is predictive of the degree of tissue atrophy at 6 months.