Total Cerebrospinal Fluid Volume Research Articles

Olfactory Bulb Volume and Asymmetry as Predictors of Executive Dysfunction in Adolescents with Congenital Heart Disease.

Common sequelae for patients with congenital heart disease (CHD) are neurodevelopmental disabilities including executive function, attention, and socio-emotional deficits. Although these are common diagnoses for patients with CHD, limited research has investigated the mechanistic underpinnings of these findings. Our previous research examined the association between abnormal respiratory ciliary motion and brain abnormalities in infants with CHD. Results suggested that abnormal ciliary motion correlated to a spectrum of subtle dysplasia, notably within the olfactory bulb (OB)1. Our current study investigates whether OB anomalies predict neurodevelopmental outcomes for pediatric patients with CHD. We hypothesize that adolescents with CHD who exhibit aberrant morphological measurements in the OB are more likely to suffer from executive functional deficits. A prospective, observational study of 54 CHD and 75 healthy subjects, ages 6-25 years old, was completed under the supervision of a senior pediatric neuroradiologist. T2 3D Space and T2 Blade 2MM MRI images were manually segmented to extract volumetric bilateral regions of the OB and cerebrospinal fluid (CSF) using ITK-SNAP. Imaging metrics were correlated to OB asymmetry, CSF to OB ratio, total CSF volume, total OB volume, and independent left and right CSF and OB volumes. Linear regression was used to evaluate MRI morphologic measurements with co-variates: CHD status, sex, MRI age, and segmenter. Executive function was determined by the Behavioral Rating Inventory of Executive Function (BRIEF) Parent Report and Delis-Kaplan Executive Function System (D-KEFS) for subjects ages 6-16. Cognition and olfactory function were measured with the NIH Toolbox Cognitive Battery and Odor Identification Test, respectively. No statistically significant results were reported between cohorts for asymmetry of OB, CSF to OB ratio, total CSF volume, total OB volume, nor between independent left and right CSF and OB volumes. Increased OB volume was associated with worse outcomes on the BRIEF Parent Report (p≤0.03). Asymmetry of OB predicted poorer executive functioning as reported by parents on the BRIEF (p≤0.05). Overall, the CHD cohort demonstrated worse scores on the BRIEF Parent Report compared to controls. Across groups, no significant association was reported for olfaction function measured by the NIH Toolbox Odor Identification Test on a limited subset of participants. As survival rates for CHD improve, there is an increased risk of long-term neurodevelopmental impairments. Our findings identify adolescents who are at risk for executive dysfunction, particularly those showing increased OB volume and/or asymmetry of the OB. This is particularly concerning for the CHD population with atypical OB morphology, who also exhibit significantly poorer outcomes on the BRIEF Parent Report and face a higher overall risk. Increased OB volume and OB asymmetry are olfactory-based biomarkers that may help identify at-risk CHD patients earlier, enabling more timely intervention and support.

Brain volume in infants with metopic synostosis: Less white matter volume with an accelerated growth pattern in early life.

Metopic synostosis patients are at risk for neurodevelopmental disorders despite a negligible risk of intracranial hypertension. To gain insight into the underlying pathophysiology of metopic synostosis and associated neurodevelopmental disorders, we aimed to investigate brain volumes of non-syndromic metopic synostosis patients using preoperative MRI brain scans. MRI brain scans were processed with HyperDenseNet to calculate total intracranial volume (TIV), total brain volume (TBV), total grey matter volume (TGMV), total white matter volume (TWMV) and total cerebrospinal fluid volume (TCBFV). We compared global brain volumes of patients with controls corrected for age and sex using linear regression. Lobe-specific grey matter volumes were assessed in secondary analyses. We included 45 metopic synostosis patients and 14 controls (median age at MRI 0.56 years [IQR 0.36] and 1.1 years [IQR 0.47], respectively). We found no significant differences in TIV, TBV, TGMV or TCBFV in patients compared to controls. TWMV was significantly smaller in patients (-62,233 mm3 [95% CI = -96,968; -27,498], Holm-corrected p = 0.004), and raw data show an accelerated growth pattern of white matter in metopic synostosis patients. Grey matter volume analyses per lobe indicated increased cingulate (1378 mm3 [95% CI = 402; 2355]) and temporal grey matter (4747 [95% CI = 178; 9317]) volumes in patients compared to controls. To conclude, we found smaller TWMV with an accelerated white matter growth pattern in metopic synostosis patients, similar to white matter growth patterns seen in autism. TIV, TBV, TGMV and TCBFV were comparable in patients and controls. Secondary analyses suggest larger cingulate and temporal lobe volumes. These findings suggest a generalized intrinsic brain anomaly in the pathophysiology of neurodevelopmental disorders associated with metopic synostosis.

Plasma Aβ level alterations after sleep deprivation correspond to brain structural remodeling in medical night shift workers

The relationship between brain structure alteration and metabolic product clearance after night shift work with total sleep deprivation (SD) remains unclear. Twenty-two intensive care unit staff on regularly rotating shift work were implemented with structural and diffusion MRI under both rest wakefulness (RW) and SD conditions. Peripheral blood samples were collected for the measurement of cerebral metabolites. Voxel-based morphometry and diffusion tensor imaging analysis were used to investigate the alterations in the gray matter density (GMD) and mean diffusivity (MD) within the participants. Furthermore, correlation analysis was performed to investigate the relationship between the neuroimaging metrics and hematological parameters. A significant increase in the GMD values was observed in the anterior and peripheral areas of the brain under SD. In contrast, a decrease in the values was observed in the posterior regions, such as the bilateral cerebellum and thalamus. In addition, a significant reduction in the total cerebrospinal fluid volume was observed under SD. The Aβ42/Aβ40 levels in participants under SD were significantly lower than those under RW. The mean MD increment values extracted from the region of interest (ROI) of the anterior brain were negatively correlated with the increment of plasma Aβ42/Aβ40 levels (r = −0.658, P = 0.008). The mean GMD decrement values extracted from the posterior ROI were positively correlated with the increment of plasma Aβ-40 levels (r = 0.601, P = 0.023). The findings of this study suggest that one night of shift work under SD induces extensive and direction-specific structural alterations of the brain, which are associated with aberrant brain metabolic waste clearance.

Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of lymphatic drainage of cerebrospinal fluid

Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15–25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice.

Cerebrospinal Fluid Production and Absorption and Ventricular Enlargement Mechanisms in Hydrocephalus.

Cerebrospinal fluid (CSF) production and absorption concept significantly changed in the early 2010s from "third circulation theory" and "classical bulk flow theory" to a whole new one as follows: First, CSF is mainly produced from interstitial fluid excreted from the brain parenchyma, and CSF produced from the choroid plexus plays an important role in maintaining brain homeostasis. Second, CSF is not absorbed in the venous sinus via the arachnoid granules, but mainly in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways at the borders attached to the choroid plexus, e.g., the inferior choroidal point of the choroidal fissure, other than the foramina of Luschka and Magendie. In idiopathic normal pressure hydrocephalus (iNPH), the lateral ventricles and basal cistern are enlarged simultaneously due to the compensatory direct CSF pathways. The average total intracranial CSF volume increased from about 150 mL at 20 years to about 350 mL at 70 years due to the decrease in brain volume with aging and further increased above 400 mL in patients with iNPH. CSF movements are composed of a steady microflow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and dynamic pulsatile flow produced by the brain and cerebral artery pulsation, respiration, and head movement. Pulsatile CSF movements might totally decrease with aging, but it in the ventricles might increase at the foramina of Magendie and Luschka dilation. Aging CSF dynamics are strongly associated with ventricular dilatation in iNPH.

480 Cerebrospinal Fluid Volume Assessed From Clinical T1w-MRI Predicts Functional Outcomes Post-Thrombectomy

INTRODUCTION: Endovascular treatment (EVT) is recognized as the standard of care for patients with acute ischemic stroke caused by large vessel occlusion (LVO). However, many patients do not achieve functional independence after successful EVT, which may be due to the pre-existing brain atrophy and higher total cerebrospinal fluid volume (CSFV). Prediction of patients who will highly benefit from EVT may be possible using baseline total CSFV as a marker of brain health and reserve. METHODS: We performed a retrospective analysis of Wake Forest Baptist Health’s Stroke Thrombectomy and Aneurysm Registry (n = 602), collected between 2015 - 2021. We selected 213 patients (mean age 67.5 ± 14.6, 49.3% female) who had adequate MRI within 14 days of EVT and a record of the modified Rankin scale (mRS) at 90 days post EVT. Clinical T1w images were transformed into high-resolution images using the convolutional neural network SynthSR. Then, FreeSurfer was used to estimate total cranial CSFV including the ventricles and choroid plexus. To correct for head size, total CSFV was adjusted to the estimated total intracranial volume. RESULTS: Baseline total CSFV significantly predicted 90-day mRS in an ordinal regression model adjusted for baseline mRS (p < 0.001). After further adjustment for age, sex, smoking history, prior stroke, hypertension, congestive heart failure, hemoglobin A1c, atrial fibrillation, ASPECT score, and other confounders, total CSFV remained an independent predictor of 90-day mRS (p = 0.007). CONCLUSIONS: This study elucidates the clinical implications of pre-existing brain health and reserve in the setting of acute ischemic strokes to aid clinicians in treatment decisions impacting prognosis. Increased total CSFV correlates with increased brain frailty and poorer functional outcomes after mechanical thrombectomy, which may ultimately attenuate its benefit.

Voxel-based morphometric magnetic resonance imaging evaluation of small head fetus: A comparative study with normal developmental fetus.

To explore the application value of voxel-based morphometric (VBM) in prenatal diagnosis of microcephaly. A retrospective study of magnetic resonance imaging of fetuses with microcephaly was performed using a single-shot fast spin echo sequence; semiautomatic segmentation of grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF); calculation of their volumes; and VBM analysis of their GM. Two independent samples t-test was used to statistically analyse the fetal GM volume in the microcephaly and normal control groups. Total intracranial volume (TIV), GM volume, WM volume, and CSF volume were linearly regressed against gestational age and compared between the two groups. In the fetus with microcephaly, GM volume of frontal lobe, temporal lobe, cuneus, anterior central gyrus, and posterior central gyrus decreased significantly (P < 0.001, corrected by family-wise error at mass level). The GM volume of microcephaly was significantly lower than that of the control group (except for 28 weeks of gestation) (P < 0.05). TIV, GM volume, WM volume, and CSF volume were all positively correlated with gestational age, and the curves in the microcephaly group were all lower than those in the control group. Compared with the normal control group, the GM volume of microcephaly fetuses decreased, and there were significant differences in many brain regions through VBM analysis.

Correlations between sleep disturbance and brain structures associated with neurodegeneration in the National Alzheimer's Coordinating Center Uniform Data Set

This study aimed to 1) determine the association between sleep disturbance and brain structure volumes, 2) the moderation effect of apolipoprotein ε4 genotype on sleep disturbance and brain structures, and 3) the moderation effect of sleep disturbance on cognitive status and regional brain volumes.Using the National Alzheimer’s Coordinating Center Uniform Data Set (n = 1,533), multiple linear regressions were used to evaluate the association between sleep disturbance and brain volumes. Sleep disturbance was measured using one question from the NPI-Q.After controlling for intracranial volume, age, sex, years of education, race, ethnicity, and applying the FDR correction, total cerebrospinal fluid volume, left lateral ventricle volume, total lateral ventricle volume, and total third ventricle volume demonstrated significantly higher means for those with sleep disturbance. Total brain volume, total white and gray matter volume, total cerebrum brain volume (including gray but not white matter), left hippocampus volume, total hippocampal volume, the left, right, and total frontal lobe cortical gray matter volume, and the left, right, and total temporal lobe cortical gray matter volume demonstrated significantly lower mean volumes for those with sleep disturbance. Sleep disturbance moderated the association between cognitive status and lateral ventricular volumes. These findings suggest that disrupted sleep is associated with atrophy across multiple brain regions and ventricular hydrocephalus ex vacuo.

The Role of Recorded Volume of Cerebrospinal Fluid Output in Predicting Modified Rankin Scale Score at Discharge in Patients with Subarachnoid Hemorrhages (DROPSS)

Introduction. External ventricular drain (EVD) placement is common among aneurysmal subarachnoid hemorrhage (aSAH). Draining cerebrospinal fluid (CSF) from the EVD is also common, yet little is known about how much to drain, the length of time to drain, or how drainage impacts patient outcomes.&#x0D; Aim. The purpose of this study is to correlate amount of CSF drainage to patient outcomes, via modified Rankin Score (mRS).&#x0D; Material and Methods. This retrospective review of data located in a local hospital-based registry and electronic medical record. A linear mixed effects model was constructed to examine CSF drainage volume as a predictor of mRS at discharge.&#x0D; Results. Data from 82 patients was included in this analysis. There was no statistically significant relationship between CSF totals and mRS at hospital discharge (p = 0.3614, r² = 0.01). After controlling for age, Hunt and Hess score, and subject as random effect, there was still no significant relationship between CSF drained and mRS score at hospital discharge (p = .9042).&#x0D; Conclusions. There is no correlation between the total volume of CSF drained and mRS at discharge. Future research should explore CSF drainage documentation practices. (JNNN 2022;11(2):43–48)&#x0D; Key Words: acute care, aneurysmal subarachnoid hemorrhage, cerebrospinal fluid, external ventricular drain, patient outcomes

Automated brain volumetric program measuring regional brain atrophy in diagnosis of mild cognitive impairment and Alzheimer's disease dementia.

A quantitative analysis of brain volume can assist in thediagnosis of Alzheimer's disease (AD) which isususally accompanied by brain atrophy. With an automated analysis program Quick Brain Volumetry (QBraVo) developed for volumetric measurements, we measured regional volumes and ratios to evaluate their performance in discriminating AD dementia (ADD) and mild cognitive impairment (MCI) patients from normal controls (NC). Validation of QBraVo was based on intra-rater and inter-rater reliability with a manual measurement. The regional volumes and ratios to total intracranial volume (TIV) and to total brain volume (TBV) or total cerebrospinal fluid volume (TCV) were compared among subjects. The regional volume to total cerebellar volume ratio named Standardized Atrophy Volume Ratio (SAVR) was calculated to compare brain atrophy. Diagnostic performances to distinguish among NC, MCI, and ADD were compared between MMSE, SAVR, and the predictive model. In total, 56 NCs, 44 MCI, and 45 ADD patients were enrolled. The average run time of QBraVo was 5min 36seconds. Intra-rater reliability was 0.999. Inter-rater reliability was high for TBV, TCV, and TIV (R = 0.97, 0.89 and 0.93, respectively). The medial temporal SAVR showed the highest performance for discriminating ADD from NC (AUC = 0.808, diagnostic accuracy = 80.2%). The predictive model using both MMSE and medial temporal SAVR improved the diagnostic performance for MCI in NC (AUC = 0.844, diagnostic accuracy = 79%). Our results demonstrated QBraVo is a fast and accurate method to measure brain volume. The regional volume calculated as SAVR could help to diagnose ADD and MCI and increase diagnostic accuracy for MCI.

Total Brain Volumetric Measures and Schizophrenia Risk: A Two-Sample Mendelian Randomization Study.

Schizophrenia (SCZ) is an idiopathic psychiatric disorder with a heritable component and a substantial public health impact. Although abnormalities in total brain volumetric measures (TBVMs) have been found in patients with SCZ, it is still unknown whether these abnormalities have a causal effect on the risk of SCZ. Here, we performed a Mendelian randomization (MR) study to investigate the possible causal associations between each TBVM and SCZ risk. Specifically, genome-wide association study (GWAS) summary statistics of total gray matter volume, total white matter volume, total cerebrospinal fluid volume, and total brain volume were obtained from the United Kingdom Biobank database (33,224 individuals), and SCZ GWAS summary statistics were provided by the Psychiatric Genomics Consortium (150,064 individuals). The main MR analysis was conducted using the inverse variance weighted method, and other MR methods, including MR-Egger, weighted median, simple mode, and weighted mode methods, were performed to assess the robustness of our findings. For pleiotropy analysis, we employed three approaches: MR-Egger intercept, MR-PRESSO, and heterogeneity tests. No TBVM was causally associated with SCZ risk according to the MR results, and no significant pleiotropy or heterogeneity was found for instrumental variables. Taken together, this study suggested that alterations in TBVMs were not causally associated with the risk of SCZ.

Cerebral structural alterations in the patients undergoing postherpetic neuralgia: A VBM-MRI study.

This study aimed to investigate the changes in gray matter (GM) volume and density in patients with postherpetic neuralgia (PHN). Using voxel-based morphometry (VBM), the differences in cerebral GM volume and concentration between 25 PHN patients and 25 healthy controls with similar gender ratios, ages, and education were compared. Meanwhile, correlation analysis was performed between the value of GM volume/concentration in the brain areas with discrepancy and the visual analog scale (VAS) score/lesion duration. The global GM volume in PHN patients was lower than that of healthy controls, while the total volume of cerebrospinal fluid in PHN patients was higher than that of healthy controls. In PHN patients, the GM volume decreased in the striatum, cerebellum, precentral gyrus, middle frontal gyrus, parahippocampal gyrus, postcentral gyrus, and so forth; the GM concentration decreased in the striatum, insula, middle and posterior cingulate, and superior temporal gyrus. There was a negative correlation between GM concentration in the right parahippocampal gyrus and the VAS in patients with PHN. In PHN patients, GM volume and density in the brain regions involved in nociceptive sensation, pain perception, and integration decreased significantly. The interaction between chronic pain of PHN and alteration of the cerebral structure may contribute to the occurrence and development of PHN.

Mechanisms of Cerebrospinal Fluid Production and Absorption and Ventricular Dilatation in Hydrocephalus

The concept of cerebrospinal fluid(CSF)production and absorption changed significantly in the early 2010s from "third circulation theory" and "classical bulk flow theory" as follows. First, CSF is mainly produced from the interstitial fluid excreted from the brain; CSF produced by the choroid plexus is important in maintaining homeostasis of the brain. Next, CSF is not absorbed in the venous sinus via the arachnoid granules, but rather in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways around the attachment of the choroid plexus other than the foramina of Luschka and Magendie. Because of the compensatory direct CSF pathways, the lateral ventricles and the basal cistern are enlarged simultaneously in idiopathic normal pressure hydrocephalus(iNPH). Due to the decrease in brain volume with aging, the average total intracranial CSF volume increases from approximately 150 mL at 20 years to approximately 350 mL at 70 years, and further increases by approximately 50-100 mL to above 400 mL in patients with iNPH. CSF movement is composed of a steady flow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and the dynamic pulsatile flow produced by the pulsation of the cerebral arteries or brain, respiration, and head movement. In general, this pulsatile CSF flow decreases with aging but increases at the opening of the foramen of Magendie and causes the ventricles to expand in iNPH.

Translational Feasibility of Lumbar Puncture for Intrathecal AAV Administration

Preclinical studies have demonstrated that a single injection of an adeno-associated virus (AAV) vector into the cerebrospinal fluid (CSF) can achieve widespread gene transfer throughout the central nervous system. Successfully translating this approach to humans requires identifying factors that influence AAV distribution in the CSF so that optimal parameters can be replicated in the clinic. In the context of developing a motor neuron-targeted gene therapy for spinal muscular atrophy, we conducted studies in nonhuman primates to evaluate the impact of injection volume on spinal cord transduction after AAV delivery via lumbar puncture. Lumbar injection of an AAVhu68 vector targeted motor neurons throughout the spinal cord, but only in juvenile nonhuman primates administered large injection volumes, equivalent to about half of the total CSF volume. Upon repeating this study with clinically relevant injection volumes and larger animals, we found that lumbar puncture failed to achieve significant transduction of the spinal cord. In contrast, vector administered into the cisterna magna distributed reproducibly throughout the spinal cord in both juvenile and adult animals. These findings highlight the challenges of translating AAV delivery via lumbar puncture to humans and suggest that delivery into the cisterna magna may represent a more feasible alternative.

Comparative Volumetric Analysis of the Brain and Cerebrospinal Fluid in Chiari Type I Malformation Patients: A Morphological Study.

Background: Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume differences between CM-I patients and normal population using a comparative volumetric analysis. Methods: 140 patients with CM-I and 140 age- and sex-matched healthy controls were included in this study. The magnetic resonance imaging (MRI) data of both groups were analyzed with an automated MRI brain morphometry system. Total intracranial, cerebrum, cerebellum, brainstem, cerebrospinal fluid (CSF), and lateral ventricle volumes as well as cerebrum and cerebellum gray/white matter (GM/WM) volumes were measured. Statistical analysis was performed. Results: Both total CSF and lateral ventricle volumes and volume percentages (Pct) were found significantly higher in CM-I patients compared to the control group. However, there were significant decreases in cerebrum and cerebellum volume Pct in CM-I patients. Although there were no significant differences in cerebrum WM volumes and volume Pct, cerebrum GM volume Pct were found to be significantly lower in CM-I patients. Conclusions: Revealing the increased CSF and lateral ventricle volume, and volume Pct supported concomitant ventricular enlargement and hydrocephalus in some CM-I patients. Decreased cerebrum GM volume Pct compared to the control group might be the underlying factor of some cortical dysfunctions in CM-I patients.

Reading deficits correlate with cortical and subcortical volume changes in a genetic migration disorder.

Periventricular nodular heterotopia (PNH) is the most common type of epileptogenic neuronal migration disorder, and often presents with epilepsy and reading disability. The functional role of ectopic nodules has been widely studied. However, the associated structural cortical and subcortical volumetric alterations have not been well characterized. Moreover, it is unknown whether a correlation between volumetric changes and behavioral problems exists.40 subjects with bilateral PNH and 40 matched healthy controls were enrolled in this study. The total cerebral, gray matter, white matter, and cerebrospinal fluid (CSF) volumes were compared between the two groups. Furthermore, structural and functional correlations were evaluated between volumetric changes and reading disability.There were no significant differences detected in total cerebral, gray matter or CSF volumes between the two groups, but there was a significant trend of larger gray-matter volume in PNH. Specifically, smaller white matter volumes were found in the PNH patients. Moreover, the volume of white matter was negatively related to time in the digit rapid naming task and a similar but insignificant trend was seen between the volume of gray matter and backward digit span.These findings suggest that reading disability exists in our sample of bilateral PNH. Periventricular nodules would have normally migrated to the overlying cortex. However, the total cerebral, gray matter, and CSF volumes were unaffected. Alterations in neuronal migration may have an impact in the white matter associated reading dysfluency, that is, visually normal.

Vascular and Neurodegenerative Markers for the Prediction of Post-Stroke Cognitive Impairment: Results from the TABASCO Study.

Stroke is a major cause of cognitive impairment and dementia. However, the underlying mechanisms beyond post-stroke cognitive impairment (PSCI) are not fully explained to date. We studied the contribution of vascular pathology measures to PSCI, separate from and in conjunction with pathologic markers associated with Alzheimer's disease (AD). Data from 397 cognitively intact ischemic stroke patients were available. All patients underwent 3T MRI and evaluated for white matter hyperintensity volume (WMHV) and integrity, ischemic lesions, small vessel disease (SVD) markers and grey matter (GM), hippocampal and cerebrospinal fluid (CSF) volumes. Comprehensive cognitive tests were performed on admission and after two years. We used multiple regression to evaluate the contributions of vascular pathology measures (Framingham risk score, WMHV, and existence of SVD) and AD-associated markers (apolipoprotein E4 status and hippocampal volume). During two years follow-up, 80 participants (20.2%) developed PSCI. Low GM and cortex volume and high WMHV and CSF volume, but not the new lesion volume, predicted the development of PSCI in a dose-dependent relationship (p = 0.001). Vascular related imaging markers and risk factors predicted PSCI better than AD related markers (p < 0.001). Brain structural measures, including total GM volume, WMHV, and CSF volume were independently associated with PSCI and may serve as early biomarkers for risk prediction. In our sample, vascular pathology measures contributed significantly better to PSCI prediction than markers associated with AD. The newly detected ischemic lesion has not emerged as biomarker for PSCI risk, thus maybe a part of the ongoing vascular pathology.

On the dispersion of a drug delivered intrathecally in the spinal canal

This paper investigates the transport of a solute carried by the cerebrospinal fluid (CSF) in the spinal canal. The analysis is motivated by the need for a better understanding of drug dispersion in connection with intrathecal drug delivery (ITDD), a medical procedure used for treatment of some cancers, infections and pain, involving the delivery of the drug to the central nervous system by direct injection into the CSF via the lumbar route. The description accounts for the CSF motion in the spinal canal, described in our recent publication (Sánchez et al., J. Fluid Mech., vol. 841, 2018, pp. 203–227). The Eulerian velocity field includes an oscillatory component with angular frequency $\unicode[STIX]{x1D714}$, equal to that of the cardiac cycle, and associated tidal volumes that are a factor $\unicode[STIX]{x1D700}\ll 1$ smaller than the total CSF volume in the spinal canal, with the small velocity corrections resulting from convective acceleration providing a steady-streaming component with characteristic residence times of order $\unicode[STIX]{x1D700}^{-2}\unicode[STIX]{x1D714}^{-1}\gg \unicode[STIX]{x1D714}^{-1}$. An asymptotic analysis for $\unicode[STIX]{x1D700}\ll 1$ accounting for the two time scales $\unicode[STIX]{x1D714}^{-1}$ and $\unicode[STIX]{x1D700}^{-2}\unicode[STIX]{x1D714}^{-1}$ is used to investigate the prevailing drug-dispersion mechanisms and their dependence on the solute diffusivity, measured by the Schmidt number $S$. Convective transport driven by the time-averaged Lagrangian velocity, obtained as the sum of the Eulerian steady-streaming velocity and the Stokes-drift velocity associated with the non-uniform pulsating flow, is found to be important for all values of $S$. By way of contrast, shear-enhanced Taylor dispersion, which is important for values of $S$ of order unity, is shown to be negligibly small for the large values $S\sim \unicode[STIX]{x1D700}^{-2}\gg 1$ corresponding to the molecular diffusivities of all ITDD drugs. Results for a model geometry indicate that a simplified equation derived in the intermediate limit $1\ll S\ll \unicode[STIX]{x1D700}^{-2}$ provides sufficient accuracy under most conditions, and therefore could constitute an attractive reduced model for future quantitative analyses of drug dispersion in the spinal canal. The results can be used to quantify dependences of the drug-dispersion rate on the frequency and amplitude of the pulsation of the intracranial pressure, the compliance and specific geometry of the spinal canal and the molecular diffusivity of the drug.

Refractive error is associated with intracranial volume

Myopia is part of the spectrum of refractive error. Myopia is associated with psychometric intelligence and, the link between brain anatomy and myopia has been hypothesized. Here we aimed to identify the associations between brain structures and refractive error in developed young adults. In a study cohort of 1,319 normal educated young adults, the refractive error showed a significant negative correlation with total intracranial volume and total cerebrospinal fluid (CSF) volume but not with total gray matter volume (GMV) or total white matter volume (WMV). Time spent studying was associated with refractive error but could not explain the aforementioned associations with brain volume parameters. The R2 values of the simple regression between spherical equivalent and outcome variables for each sex in non-whole brain imaging analyses were less than 0.05 in all cases and thus were weak. Psychometric intelligence was not associated with refractive error or total CSF volume, but it weakly positively correlated with total GMV and total WMV in this study population. Thus, refractive error appears to be primarily (weakly) associated with the volume of the cranium, whereas psychometric intelligence was associated with the volume of the brain.

A 3D subject-specific model of the spinal subarachnoid space with anatomically realistic ventral and dorsal spinal cord nerve rootlets

BackgroundThe spinal subarachnoid space (SSS) has a complex 3D fluid-filled geometry with multiple levels of anatomic complexity, the most salient features being the spinal cord and dorsal and ventral nerve rootlets. An accurate anthropomorphic representation of these features is needed for development of in vitro and numerical models of cerebrospinal fluid (CSF) dynamics that can be used to inform and optimize CSF-based therapeutics.MethodsA subject-specific 3D model of the SSS was constructed based on high-resolution anatomic MRI. An expert operator completed manual segmentation of the CSF space with detailed consideration of the anatomy. 31 pairs of semi-idealized dorsal and ventral nerve rootlets (NR) were added to the model based on anatomic reference to the magnetic resonance (MR) imaging and cadaveric measurements in the literature. Key design criteria for each NR pair included the radicular line, descending angle, number of NR, attachment location along the spinal cord and exit through the dura mater. Model simplification and smoothing was performed to produce a final model with minimum vertices while maintaining minimum error between the original segmentation and final design. Final model geometry and hydrodynamics were characterized in terms of axial distribution of Reynolds number, Womersley number, hydraulic diameter, cross-sectional area and perimeter.ResultsThe final model had a total of 139,901 vertices with a total CSF volume within the SSS of 97.3 cm3. Volume of the dura mater, spinal cord and NR was 123.1, 19.9 and 5.8 cm3. Surface area of these features was 318.52, 112.2 and 232.1 cm2 respectively. Maximum Reynolds number was 174.9 and average Womersley number was 9.6, likely indicating presence of a laminar inertia-dominated oscillatory CSF flow field.ConclusionsThis study details an anatomically realistic anthropomorphic 3D model of the SSS based on high-resolution MR imaging of a healthy human adult female. The model is provided for re-use under the Creative Commons Attribution-ShareAlike 4.0 International license (CC BY-SA 4.0) and can be used as a tool for development of in vitro and numerical models of CSF dynamics for design and optimization of intrathecal therapeutics.