Total CSF Volume Research Articles

Magnitude and kinetics of a set of neuroanatomic volume and thickness together with white matter hyperintensity is definitive of cognitive status and brain age

Even among the subjects classified as cognitively normal, there exists a subset of individuals at a given chronological age (CA) who harbor white matter hyperintensity (WMH) while another subset presents with low or undetectable WMH. Here, we conducted a comprehensive MRI segmentation of neuroanatomic structures along with WMH quantification in groups of cognitively normal (CN), cognitively impaired (CI) individuals, and individuals with an etiological diagnosis of cognitive impairment owing to Alzheimer’s Disease (CI-AD) across the early (50–64 years), intermediate (65–79 years), and late (≥80 years) age groups from the NACC cohort. Neuroanatomic volumetry quantification revealed that thinning of the parahippocampal gyrus in the early (p = 0.016) and intermediate age groups (p = 0.0001) along with an increase in CSF (p = 0.0009) delineates between CI and CI-AD subjects. Although, a significant loss of ~5–10% in volume of gray matter (p(CN vs CI) < 0.0001, p(CN vs CI-AD) < 0.0001), white matter (p(CN vs CI) = 0.002, p(CN vs CI-AD) = 0.0003) and hippocampus (p(CN vs CI) = 0.007, p(CN vs CI-AD) < 0.0001) was evident at the early age groups in the CI and CI-AD compared to CN but it was not distinct between CI and CI-AD. Using the neuroanatomic and WMH volume, and the supervised decision tree-based ML modeling, we have established that a minimum set of Three brain quantities; Total brain (GM + WM), CSF, and WMH volume, provide the Optimal quantitative features discriminative of cognitive status as CN, CI, and CI-AD. Furthermore, using the volume/thickness of 178 neuroanatomic structures, periventricular and deep WMH volume quantification for the 819 CN subjects, we have developed a quantitative index as ‘Brain Age’ (BA) depictive of neuroanatomic health at a given CA. Subjects with elevated WMH load (5–10 ml) had increased BA ( + 0.6 to +4 years) than the CA. Increased BA in the subjects with elevated WMH is suggestive of WMH-induced vascular insult leading to accelerated and early structural loss than expected for a given CA. Henceforth, this study establishes that quantification of WMH together with an optimal number of neuroanatomic features is mandatory to delve into the biological underpinning of aging and aging-associated cognitive disorders.

Sodium signal intensity of CSF using 1H-guided 23Na-MRI as a potential noninvasive biomarker in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and mnestic deficits. The pathophysiology of AD is not fully understood, which renders the development of accurate tools for early diagnosis and effective therapies exceedingly difficult. In this study, we investigated the use of 23Na-MRI to measure the relative sodium signal intensities (rSSIs) in CSF in patients with AD and healthy controls. We prospectively recruited 11 patients with biomarker-diagnosed early-stage AD, as well as 12 cognitively healthy age-matched controls. All participants underwent 23Na-MRI to measure rSSI. Statistical analyses were performed to compare CSF sodium signal intensities between groups and to evaluate the specificity and sensitivity of the rSSI in the diagnosis of AD. RSSIs in CSF were significantly higher in AD patients (mean=68.6%±7.7%) compared to healthy controls (mean=56.9%±5.5%) (p<.001). There was also a significant negative correlation between rSSI in CSF and hippocampus and amygdala volumes (r=-.54 and -.49, p<.05) as well as a positive correlation with total CSF volumes (r=.81, p<.05). Receiver operating characteristic analysis showed high diagnostic accuracy for rSSI in discriminating between AD patients and healthy controls (area under the curve=.94). Our study provides evidence that rSSI in CSF is increased in AD patients in comparison to healthy controls. rSSI may serve as a potential marker for early detection and monitoring of disease progression. Larger, longitudinal studies are needed to confirm our findings and to investigate the association between rSSI in CSF and the severity of cognitive impairment.

Mediterranean diet protects against neuroinflammation and degeneration in female nonhuman primates

AbstractBackgroundMediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets in part by protecting against neuroinflammation. In middle‐aged humans that subsequently develop AD, increased cortical thickness precedes atrophy. It is hypothesized that the initial increase in brain volumes may be due to early neuroinflammation that precedes neurodegeneration (Pegueroles et al. Alzheimers Dement 2017). Long term impacts of diet patterns on health are difficult to quantify in human beings. Thus, we addressed this hypothesis in cynomolgus macaques (Macaca fascicularis), a nonhuman primate that undergoes age‐related changes in brain structure and function, and responds to Western diets, like humans.Method38 middle‐aged (mean = 12 years of age) female macaques were fed a Western or Mediterranean diet for 2.5 years in a randomized nonhuman primate trial. Changes from baseline in volumes of total brain, gray, cortical gray, and white matter, cerebrospinal fluid and (CSF), were determined by structural MRI. We also generated thickness‐based AD temporoparietal meta‐ROIs based on the AD clinical literature as previously described (Frye et al., 2021 Alzheimers Dement. 2021;17:733). Transcriptional profiles in the temporal cortex were determined at the end of the study by RNAseq.ResultWestern diet led to increases in temporoparietal cortical thicknesses, total brain and gray matter volumes, and diminished cerebrospinal fluid and white matter volumes. Diet significantly altered expression of seven genes (FDR&lt;0.05). The Mediterranean group had lower expression of CDK14, a proinflammatory regulator, and higher expression of BTN2A1, KATNB1, LFNG, MRC2, SLCA32, and TMEM268, many of which have anti‐inflammatory associations. Several differentially expressed genes were correlated with AD‐relevant brain volumes. CDK14 was positively correlated with total brain, total gray, and cortical gray matter volumes and temporoparietal cortical thickness (Figure, Mediterranean = yellow), and negatively correlated with total white matter and CSF volumes. LFNG, MRC2, and SLCA32 were negatively correlated with total brain, total gray, and cortical gray matter volume, as well as temporoparietal cortical thickness, and positively correlated with CSF volume (all p’s&lt;0.05).ConclusionThese results suggest that the Mediterranean diet protects against, whereas the Western diet promotes, AD‐relevant neuroinflammation associated with early increases in gray matter volumes.

Use of cortical volume to predict response to temporary CSF drainage in patients with idiopathic normal pressure hydrocephalus.

Temporary drainage of CSF with lumbar puncture or lumbar drainage has a high predictive value for identifying patients with suspected idiopathic normal pressure hydrocephalus (iNPH) who may benefit from ventriculoperitoneal shunt insertion. However, it is unclear what differentiates responders from nonresponders. The authors hypothesized that nonresponders to temporary CSF drainage would have patterns of reduced regional gray matter volume (GMV) as compared with those of responders. The objective of the current investigation was to compare regional GMV between temporary CSF drainage responders and nonresponders. Machine learning using extracted GMV was then used to predict outcomes. This retrospective cohort study included 132 patients with iNPH who underwent temporary CSF drainage and structural MRI. Demographic and clinical variables were examined between groups. Voxel-based morphometry was used to calculate GMV across the brain. Group differences in regional GMV were assessed and correlated with change in results on the Montreal Cognitive Assessment (MoCA) and gait velocity. A support vector machine (SVM) model that used extracted GMV values and was validated with leave-one-out cross-validation was used to predict clinical outcome. There were 87 responders and 45 nonresponders. There were no group differences in terms of age, sex, baseline MoCA score, Evans index, presence of disproportionately enlarged subarachnoid space hydrocephalus, baseline total CSF volume, or baseline white matter T2-weighted hyperintensity volume (p > 0.05). Nonresponders demonstrated decreased GMV in the right supplementary motor area (SMA) and right posterior parietal cortex as compared with responders (p < 0.001, p < 0.05 with false discovery rate cluster correction). GMV in the posterior parietal cortex was associated with change in MoCA (r2 = 0.075, p < 0.05) and gait velocity (r2 = 0.076, p < 0.05). Response status was classified by the SVM with 75.8% accuracy. Decreased GMV in the SMA and posterior parietal cortex may help identify patients with iNPH who are unlikely to benefit from temporary CSF drainage. These patients may have limited capacity for recovery due to atrophy in these regions that are known to be important for motor and cognitive integration. This study represents an important step toward improving patient selection and predicting clinical outcomes in the treatment of iNPH.

Predictive value of spinal CSF volume in the preoperative assessment of patients with idiopathic normal-pressure hydrocephalus.

The pathophysiology, diagnosis, and management of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Although some prognostic tests recommended in iNPH guidelines should have high sensitivity and high predictive value, there is often no positive clinical response to surgical treatment. In our study, 19 patients with clinical and neuroradiological signs of iNPH were selected for preoperative evaluation and possible further surgical treatment according to the guidelines. MR volumetry of the intracranial and spinal space was performed. Patients were exposed to prolonged external lumbar drainage in excess of 10 ml per hour during 3 days. Clinical response to lumbar drainage was assessed by a walk test and a mini-mental test. Twelve of 19 patients showed a positive clinical response and underwent a shunting procedure. Volumetric values of intracranial space content in responders and non-responders showed no statistically significant difference. Total CSF volume (sum of cranial and spinal CSF volumes) was higher than previously published. No correlation was found between spinal canal length, CSF pressure, and CSF spinal volume. The results show that there is a significantly higher CSF volume in the spinal space in the responder group (n = 12) (120.5 ± 14.9 ml) compared with the non-responder group (103.1 ± 27.4 ml; n = 7). This study demonstrates for the first time that CSF volume in the spinal space may have predictive value in the preoperative assessment of iNPH patients. The results suggest that patients with increased spinal CSF volume have decreased compliance. Additional prospective randomized clinical trials are needed to confirm our results.

SOC-I-10 MRI Investigations of total and local CSF volumes in juvenile and mature nonhuman primates for the preclinical safety assessment of antisense oligonucleotides

SOC-I-10 MRI Investigations of total and local CSF volumes in juvenile and mature nonhuman primates for the preclinical safety assessment of antisense oligonucleotides

Intracranial compartment volumes and their distribution among clinically diagnosed patients with normal pressure hydrocephalus and brain atrophy in a Nigerian population

Normal pressure hydrocephalus is a form of non-obstructive hydrocephalus characterized by the triad of symptoms. These symptoms are typical or atypical. Because of its potential reversibility, researchers have paid attention to its diagnosis and in differentiating it with other forms of dementia such as brain atrophy. To determine the intracranial compartment volumes and their differences among patients with NPH and Brain Atrophy (BA). This was a cross-sectional study involving consenting patients diagnosed with NPH and BA who were referred for routine brain CT. Medical conditions known to influence intracranial volume were excluded. Age -matched normal control were clinically and radiologically confirmednormal and were also recruited. Intracranial volumes and CSF distribution determination was based on Cavalieri test point computation principle. Test point summation was on a locally developed software for this purpose. Overall, the values of BA recorded higher mean values for most of the intracranial compartment volumes. Intraventricular volume was consistently higher in NPH groups. Statistical difference exists among intraventricular and total intracranial CSF volume across patients with BA, NPH and control. A post hoc test revealed control-NPH comparison across these variables. Control-BA comparison was evident in total intracranial CSF volume only. Higher mean values of intracranialcompartment volumes were observed in patients with BA than among patients with NPH and their control. Anthropometric indices did not show any difference between patients with BA, NPH and their control. These indices can be used as basis in objectively differentiating NPH from BA.

Upright versus supine MRI: effects of body position on craniocervical CSF flow

BackgroundCerebrospinal fluid (CSF) circulation between the brain and spinal canal, as part of the glymphatic system, provides homeostatic support to brain functions and waste clearance. Recently, it has been observed that CSF flow is strongly driven by cardiovascular brain pulsation, and affected by body orientation. The advancement of MRI has allowed for non-invasive examination of the CSF hydrodynamic properties. However, very few studies have addressed their relationship with body position (e.g., upright versus supine). It is important to understand how CSF hydrodynamics are altered by body position change in a single cardiac phase and how cumulative long hours staying in either upright or supine position can affect craniocervical CSF flow.MethodsIn this study, we investigate the changes in CSF flow at the craniocervical region with flow-sensitive MRI when subjects are moved from upright to supine position. 30 healthy volunteers were imaged in upright and supine positions using an upright MRI. The cranio-caudal and caudo-cranial CSF flow, velocity and stroke volume were measured at the C2 spinal level over one cardiac cycle using phase contrast MRI. Statistical analysis was performed to identify differences in CSF flow properties between the two positions.ResultsCSF stroke volume per cardiac cycle, representing CSF volume oscillating in and out of the cranium, was ~ 57.6% greater in supine (p < 0.0001), due to a ~ 83.8% increase in caudo-cranial CSF peak velocity during diastole (p < 0.0001) and extended systolic phase duration when moving from upright (0.25 ± 0.05 s) to supine (0.34 ± 0.08 s; p < 0.0001). Extrapolation to a 24 h timeframe showed significantly larger total CSF volume exchanged at C2 with 10 h spent supine versus only 5 h (p < 0.0001).ConclusionsIn summary, body position has significant effects on CSF flow in and out of the cranium, with more CSF oscillating in supine compared to upright position. Such difference was driven by an increased caudo-cranial diastolic CSF velocity and an increased systolic phase duration when moving from upright to supine position. Extrapolation to a 24 h timeframe suggests that more time spent in supine position increases total amount of CSF exchange, which may play a beneficial role in waste clearance in the brain.

A-06 MRI and Neuropsychological Change During Conversion from Normal/MCI to Alzheimer’s Disease

Abstract Objective Analyze neurocognitive and structural brain changes associated with conversion from normal cognition/MCI to Alzheimer’s disease (AD). Method Thirty-two participants from the National Alzheimer’s Coordinating Center included 22 women; mean (SD): age = 77.06 (8.1); education = 14.59 (3.5). All had either normal cognition or MCI at first visit when MRI was obtained and were diagnosed with AD at follow-up MRI; mean time between MRI’s = 4.1 years. Imaging of Dementia &amp; Aging lab performed calculations for MRI structural change using Linux-based software. Participants took neuropsychological tests within three months of each MRI visit. Results MRI structural degeneration occurred in: left (d = .46) and right (d = .47) entorhinal cortical thickness; left (d = .82) and right (d = .95) hippocampal volume; left (d = .74) and right (d = .43) middle temporal gray matter volume; left parahippocampal cortical thickness (d = .55); total white matter volume (d = .55); total brain volume (d = .78); and total CSF volume (d = 1.14). Significant neuropsychological decline included Animal fluency (d = 1.02), Vegetable fluency (d = .69), Digit Symbol (d = .53), Trails B (d = .42), and Digit Span Backward (d = .56). There was not a significant change in Logical Memory. Conclusions Participants who converted from normal cognition/MCI to AD showed MRI degeneration in medial temporal structures as well as generalized atrophy and white matter loss. These structural changes accompanied a significant decline in semantic verbal fluency, working memory, and processing speed. There was not a significant change in verbal memory.

Planar single plane area determination is a viable substitute for total volumetry of CSF and brain in childhood hydrocephalus.

In the treatment of childhood hydrocephalus, 3D volumetry seems to have many advantages over classical planar index measurements for dedicated monitoring of changes in cerebrospinal fluid and brain volume. Nevertheless, this method requires extensive technical effort and access to the complete three-dimensional data set. Against this background, we evaluated the possibility of planar area determination in a single plane and the correlation to volumetry. 138 routinely performed true FISP MRI sequences (1mm isovoxel) were analyzed retrospectively in 68 patients with pediatric hydrocephalus. After preprocessing, the 3D-data sets were skull stripped to estimate the inner skull volume. A 2-class segmentation into different tissue types (brain matter and CSF) was performed, and the volumes of CSF (VCSF) and brain matter (VBrain) were calculated. A plane at the level of the foramina of Monro was manually identified in the ac-pc oriented data. In this plane, the areas of brain (ABrain) and CSF (ACSF) in cm2 were calculated and used for further correlation analysis. Mean VCSF was 340 ± 145cm3 and VBrain 1173 ± 254cm3. In the selected plane, ACSF was 26 ± 14cm2, and ABrain was 107 ± 25cm2. There was a very strong positive correlation between both ACSF and VCSF (r = 0.895) and between ABrain and VBrain (r = 0.846). The prediction equations for VBrain and VCSF were highly significant. Planar area determination of brain and CSF correlates excellently with both VCSF and VBrain. Thus, areas can serve as a surrogate marker for total brain and CSF volumes for a quantitated objective tracking of changes during treatment of childhood hydrocephalus.

Large Volume Intrathecal Bolus: CSF Pressure and Implications for Safety

ObjectivesLarge volume intrathecal (IT) bolus administrations yield an efficient method of therapeutic delivery to the cerebral CSF from a clinically accessible injection site. In non‐human primates, high volume bolus can translocate up to 90% of the administered substance to the cerebro‐cervical CSF immediately. It is known that administration of up to ca. 20% of the total CSF volume is safe for humans and monkeys; however, the safety parameters detailing the volume and underlying mechanistic limits have not been studied. The goal of the present work is to characterize the relationship between administered volumes and rates and intracranial pressure (ICP) as a safety parameter in rats and monkeys.MethodsICP was measured in the cisterna magna (rats) and the subcutaneous injection port leading to the lumbar CSF (monkeys) utilizing a 1F piezoresistive diffused semiconductor pressure sensor mounted at the tip of a 20 cm long 0.8 F polyimide catheter (Millar, Inc). Signal processing was carried out using a FE221 Bridge Amplifier coupled with a PowerLab 4/35 (ADInstruments). Control of both modules and waveform analysis was performed using LabChart 8 software (ADInstruments).ResultsICP in rats and monkeys was characterized by a periodic waveform of classical shape with spectrally resolved P1, P2, and P3 components (Fig. 1). Mean baseline ICP in rats was 9.3±2.3 mmHg. The adaptability of rats to varying ICPs was studied by plotting the time‐averaged amplitude of the P1 component against the mean ICP. Correlation between these two variables formed three distinctive zones: (1) low synchronization (good compensatory reserve) at low ICP, (2) good synchronization (poor compensatory reserve) at higher ICP, and (3) negative correlation (impaired compensatory mechanisms) at ICP &gt; 32.3±6.5 mmHg (Fig. 1). The determined terminally “critical” ICP was then used to ascertain safe infusion rates and volumes in a separate group of rats. We found that infusion rates of up to 40 mkL/min could be used to safely administer volumes of at least 50% of CSF volume, whereas significantly smaller volumes could be infused at higher rates (Fig. 2). Our previous studies showed that monkeys tolerated bolus injections of 0.5 mL/kg body weight given at ca. 2 mL/min. Administration of this volume in a group of N=4 resulted in an ICP elevation by 47.5±5.9 mmHg. In rats and monkeys, the elevated post‐bolus ICP exponentially relaxed to the baseline within 11.3±8.1 min and 12.3±8.1 min, respectively.ConclusionsICP is a function of the rate and volume of fluid administration in the CSF and can safely be tolerated up to 32.3±6.5 mmHg (3.5‐fold) in rats. Comparable ICP relaxation times in monkeys and rats suggest similarities in the mechanisms of volume accommodation (hydrostatic compliance in the cervical region) and ICP adaptation (likely accelerated CSF drainage). The obtained data can improve the prediction of the safety of large‐volume IT drug administration and can be instrumental for identifying mechanisms regulating ICP adaptability.Support or Funding InformationThis study was supported by MGH ECOR Formulaic Award (2015) and NIH grants R01NS092838 and R21NS090049.

Automated segmentation of MR imaging to determine normative central nervous system cerebrospinal fluid volumes in healthy volunteers

An accurate non-invasive method to determine total body cerebrospinal fluid volume has a number of potential diagnostic and therapeutic applications. Herein we describe a technique for automated segmentation of total body MRI data to determine cranial and spinal CSF volume in 15 healthy adults. These in vivo estimates of CSF volume exceed the standard reported volume of 150mL in human adults and provide normative data for diagnosis of disease states such as hydrocephalus and therapy including pharmacologic dosimetry. No correlation was observed between patient height or weight and total body CSF volume.

Quantitative MRI for Rapid and User-Independent Monitoring of Intracranial CSF Volume in Hydrocephalus.

Quantitative MR imaging allows segmentation of different tissue types and automatic calculation of intracranial volume, CSF volume, and brain parenchymal fraction. Brain parenchymal fraction is calculated as (intracranial volume - CSF volume) / intracranial volume. The purpose of this study was to evaluate whether the automatic calculation of intracranial CSF volume or brain parenchymal fraction could be used as an objective method to monitor volume changes in the ventricles. A lumbar puncture with drainage of 40 mL of CSF was performed in 23 patients under evaluation for idiopathic normal pressure hydrocephalus. Quantitative MR imaging was performed twice within 1 hour before the lumbar puncture and was repeated 30 minutes, 4 hours, and 24 hours afterward. For each time point, the volume of the lateral ventricles was manually segmented and total intracranial CSF volume and brain parenchymal fraction were automatically calculated by using Synthetic MR postprocessing. At 30 minutes after the lumbar puncture, the volume of the lateral ventricles decreased by 5.6 ± 1.9 mL (P < .0001) and the total intracranial CSF volume decreased by 11.3 ± 5.6 mL (P < .001), while brain parenchymal fraction increased by 0.78% ± 0.41% (P < .001). Differences were significant for manual segmentation and brain parenchymal fraction even at 4 hours and 24 hours after the lumbar tap. There was a significant association using a linear mixed model between change in manually segmented ventricular volume and change in brain parenchymal fraction and total CSF volume, (P < .0001). Brain parenchymal fraction is provided rapidly and fully automatically with Synthetic MRI and can be used to monitor ventricular volume changes. The method may be useful for objective clinical monitoring of hydrocephalus.

Is the Penney Burden of Pathology (BOP) Score a Reasonable Index of Disease Severity in Premanifest HD (preHD)? (P06.035)

Objective: To investigate the validity of the Penney Burden of Pathology (BOP) score (Age X [CAG length-35.5]) (Penney et al, 1997) as a measure of disease severity in premanifest HD (preHD). We also compare the BOP9s utility with other preHD burden measures, namely the Aylward (Aylward et al, 2004) and Langbehn (Langbehn et al, 2010) years-to-onset (YTO) estimates. Background Although developed in 1997 from post-mortem analysis of striatal atrophy in 89 Huntington9s patients, the BOP has never been validated as a useful preHD burden measure. Despite this, a number of recent preHD studies have used this score for inclusion criteria for subjects in clinical trials. Design/Methods: 37 preHD subjects (mean age 41.2, mean CAG repeat length 42.3) underwent 1.5T T1-weighted structural imaging. Automated segmentation methods (Stoffers et al, 2010; Majid et al, in press) were used to determine normalized volumes for the whole brain, gray matter, white matter, cerebrospinal fluid, subcortical nuclei (caudate and putamen), and various cortical regions. These measures were then correlated with the BOP, in addition to Aylward and Langbehn YTO estimates. Results: BOP correlated with total brain (R=-.36, p=.03), gray matter (R=-.38, p=.02), ventricular CSF (R=.52, p=.001), and putamen (R=-.39, p=.02) volumes but not significantly with either caudate (R=-.30, p=.07) or cortical volumes. Correlations with the Langbehn YTO estimate were similar. By contrast, the Aylward YTO more strongly predicted atrophy in all the above regions, in addition to the caudate (R=.53, p=.001) and also a number of specific cortical areas. Conclusions: Comparison of various preHD burden measures suggests that the Aylward YTO estimate may be a better predictor of structural atrophy, possibly because of the addition of parental age-of-onset, which may comprise genetic and environmental factors unaccounted for by CAG repeat length alone. Caution should be exercised in selecting preHD subjects for clinical trials solely on the basis of BOP score. Supported by: CHDI. Disclosure: Dr. Majid has nothing to disclose. Dr. Stoffers has nothing to disclose. Dr. Anders has received personal compensation for activities with CorTech Labs. Dr. Anders holds stock and/or stock options in CorTechs Labs, Inc. Dr. Goldstein has nothing to disclose. Dr. Aron has nothing to disclose. Dr. Corey-Bloom has received personal compensation for activities with Isis Pharmaceuticals as a consultant. Dr. Corey-Bloom has received research support from Medivation, Pfizer Inc, Elan Corporation, Forest Laboratories, Inc., Teva Neuroscience, NeuroSearch, and CHDI.

Developmental change in regional brain structure over 7 months in early adolescence: Comparison of approaches for longitudinal atlas-based parcellation

Early adolescence is a time of rapid change in neuroanatomy and sexual development. Precision in tracking changes in brain morphology with structural MRI requires image segmentation with minimal error. Here, we compared two approaches to achieve segmentation by image registration with an atlas to quantify regional brain structural development over a 7-month interval in normal, early adolescent boys and girls. Adolescents were scanned twice (average interval=7.3 months), yielding adequate data for analysis in 16 boys (baseline age 10.9 to 13.9 years; Tanner Stage=1 to 4) and 12 girls (baseline age=11.2 to 13.7 years; Tanner Stage=3 to 4). Brain volumes were derived from T1-weighted (SPGR) images and dual-echo Fast Spin-Echo (FSE) images collected on a GE 3T scanner with an 8-channel phased-array head coil and analyzed by registration-based parcellation using the SRI24 atlas. The "independent" method required two inter-subject registrations: both baseline (MRI 1) to atlas and follow-up (MRI 2) to the atlas. The "sequential" method required one inter-subject registration, which was MRI 1 to the atlas, and one intra-subject registration, which was MRI 2 to MRI 1. Gray matter/white matter/CSF were segmented in both MRI-1 and MRI-2 using FSL FAST with tissue priors also based on the SRI24 atlas. Gray matter volumes were derived for 10 cortical regions, gray+white matter volumes for 5 subcortical structures, and CSF volumes for 4 ventricular regions and the cortical sulci. Across the 15 tissue regions, the coefficient of variation (CV) of change scores across individuals was significantly lower for the sequential method (CV=3.02), requiring only one inter-subject registration, than for the independent method (CV=9.43), requiring two inter-subject registrations. Volume change based on the sequential method revealed that total supratentorial and CSF volumes increased, while cortical gray matter volumes declined significantly (p<0.01) in anterior (lateral and medial frontal, anterior cingulate, precuneus, and parietal) but not posterior (occipital, calcarine) cortical regions. These volume changes occurred in all boys and girls who advanced a step in Tanner staging. Subcortical structures did not show consistent changes. Thus, longitudinal MRI assessment using robust registration methods is sufficiently sensitive to identify significant regional brain changes over a 7-month interval in boys and girls in early adolescence. Increasing the temporal resolution of the retest interval in longitudinal developmental studies could increase accuracy in timing of peak growth of regional brain tissue and refine our understanding of the neural mechanisms underlying the dynamic changes in brain structure throughout adolescence.

A novel quantitative simple brain metric using MR imaging for preterm infants.

The application of volumetric techniques to preterm infants has revealed brain volume reductions. Such quantitative data are not available in routine neonatal radiologic care. The objective of this study was to develop simple brain metrics to compare brain size in preterm and term infants and to correlate these metrics with brain volumes from volumetric MR imaging techniques. MR images from 189 preterm infants <30 weeks' gestational age or <1250 g birthweight scanned at term-equivalent age and 36 term infants were studied. Fifteen tissue and fluid measures were systematically evaluated on 4 selected sections. The results were correlated with total brain, gray matter, white matter, and CSF volumes. The mean bifrontal, biparietal, and transverse cerebellar diameters were reduced (-11.6%, 95% confidence interval [CI], -13.8% to -9.3%; -12%, 95% CI, -14% to -9.8%; and -8.7%, 95% CI, -10.5% to -7% respectively) and the mean left ventricle diameter was increased (+22.3%, 95% CI, 2.9%-41.6%) in preterm infants (P < .01). Strong correlations were found between the bifrontal and biparietal measures with total brain tissue volume, whereas the size of the ventricles and the interhemispheric measure correlated with CSF volume. Intraobserver reliability was high (intraclass correlation coefficients [ICC], >0.7), where interobserver agreement was acceptable for tissue measures (ICC, >0.6) but lower for fluid measures (ICC, <0.4). Simple brain metrics at term-equivalent age showed smaller brain diameters and increased ventricle size in preterm infants compared with full-term infants. These measures represent a reliable and easily applicable method to quantify brain growth and assess brain atrophy in this at-risk population.

Effect of Endovascular Hypothermia on Acute Ischemic Edema: Morphometric Analysis of the ICTuS Trial

Pilot studies of hypothermia for stroke suggest a potential benefit in humans. We sought to test whether hypothermia decreases post-ischemic edema using CT scans from a pilot trial of endovascular hypothermia for stroke. Eighteen patients with acute ischemic stroke underwent therapeutic hypothermia (target = 33 degrees C) for 12 or 24 h followed by a 12-h controlled re-warm using an endovascular system. CT scans obtained at baseline, 36-48 h (right after cooling and re-warming) and 30 days were digitized, intracranial compartment volumes measured using a validated stereological technique, and the calculated change in CSF volume between the three time-points were used as an estimate of edema formation in each patient. Patients were grouped retrospectively for analysis based on whether they cooled effectively (i.e., to a temperature nadir of less than 34.5 degrees C within 8 h) or not. Eleven patients were cooled partially or not at all, and seven were effectively cooled. Baseline demographics and compartment volumes and densities were similar in both groups. At 36-48 h, the total CSF volume had significantly decreased in the not-cooled group compared to the cooled group (P < 0.05), with no significant difference in mean volume of ischemia between them (73 +/- 73 ml vs. 54 +/- 59 ml, respectively), suggesting an ameliorative effect of hypothermia on acute edema formation. At 30 days, the difference in CSF volumes had resolved, and infarct volumes (73 +/- 71 ml vs. 84 +/- 102 ml, respectively) and functional outcomes were comparable. Endovascular hypothermia decreases acute post-ischemic cerebral edema. A larger trial is warranted to determine if it affects final infarct volume and outcome in stroke.

P2-181 Regionally specific atrophy of the corpus callosum in Alzheimer's disease and mild cognitive impairment

Early adolescence is a time of rapid change in neuroanatomy and sexual development. Precision in tracking changes in brain morphology with structural MRI requires image segmentation with minimal error. Here, we compared two approaches to achieve segmentation by image registration with an atlas to quantify regional brain structural development over a 7-month interval in normal, early adolescent boys and girls. Adolescents were scanned twice (average interval = 7.3 months), yielding adequate data for analysis in 16 boys (baseline age 10.9 to 13.9 years; Tanner Stage = 1 to 4) and 12 girls (baseline age = 11.2 to 13.7 years; Tanner Stage = 3 to 4). Brain volumes were derived from T1-weighted (SPGR) images and dual-echo Fast Spin-Echo (FSE) images collected on a GE 3 T scanner with an 8-channel phased-array head coil and analyzed by registration-based parcellation using the SRI24 atlas. The “independent” method required two inter-subject registrations: both baseline (MRI 1) to atlas and follow-up (MRI 2) to the atlas. The “sequential” method required one inter-subject registration, which was MRI 1 to the atlas, and one intra-subject registration, which was MRI 2 to MRI 1. Gray matter/white matter/CSF were segmented in both MRI-1 and MRI-2 using FSL FAST with tissue priors also based on the SRI24 atlas. Gray matter volumes were derived for 10 cortical regions, gray + white matter volumes for 5 subcortical structures, and CSF volumes for 4 ventricular regions and the cortical sulci. Across the 15 tissue regions, the coefficient of variation (CV) of change scores across individuals was significantly lower for the sequential method (CV = 3.02), requiring only one inter-subject registration, than for the independent method (CV = 9.43), requiring two inter-subject registrations. Volume change based on the sequential method revealed that total supratentorial and CSF volumes increased, while cortical gray matter volumes declined significantly (p < 0.01) in anterior (lateral and medial frontal, anterior cingulate, precuneus, and parietal) but not posterior (occipital, calcarine) cortical regions. These volume changes occurred in all boys and girls who advanced a step in Tanner staging. Subcortical structures did not show consistent changes. Thus, longitudinal MRI assessment using robust registration methods is sufficiently sensitive to identify significant regional brain changes over a 7-month interval in boys and girls in early adolescence. Increasing the temporal resolution of the retest interval in longitudinal developmental studies could increase accuracy in timing of peak growth of regional brain tissue and refine our understanding of the neural mechanisms underlying the dynamic changes in brain structure throughout adolescence.

Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study.

The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents.

Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study

The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High‐resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age‐related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray‐matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white‐matter proportion was significantly greater than the change in total cerebral gray‐matter proportion over this age range, suggesting that the relative gray‐matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age‐related differences in gray and white matter in normally developing children and adolescents.