Cross-sectional volumes and trajectories of the human brain, gray matter, white matter and cerebrospinal fluid in 9,473 typically aging adults

Accurate knowledge of adult human brain volume (BV) is critical for studies of aging- and disease-related brain alterations, and for monitoring the trajectories of neural and cognitive functions in conditions like Alzheimer’s disease and traumatic brain injury. This scoping meta-analysis aggregates normative reference values for BV and three related volumetrics—gray matter volume (GMV), white matter volume (WMV) and cerebrospinal fluid volume (CSFV)—from typically-aging adults studied cross-sectionally using magnetic resonance imaging (MRI). Drawing from an aggregate sample of 9,473 adults, this study provides (A) regression coefficients β describing the age-dependent trajectories of volumetric measures by sex within the range from 20 to 70 years based on both linear and quadratic models, and (B) average values for BV, GMV, WMV and CSFV at the representative ages of 20 (young age), 45 (middle age) and 70 (old age). The results provided synthesize ∼20 years of brain volumetrics research and allow one to estimate BV at any age between 20 and 70. Importantly, however, such estimates should be used and interpreted with caution because they depend on MRI hardware specifications (e.g. scanner manufacturer, magnetic field strength), data acquisition parameters (e.g. spatial resolution, weighting), and brain segmentation algorithms. Guidelines are proposed to facilitate future meta- and mega-analyses of brain volumetrics.Disclosure statementThe author declares that he has no actual or potential conflicts of interest.

ASSESSING BRAIN VOLUMETRICS IN THE AGING BRAIN USING COMPUTED TOMOGRAPHY

Although broadly utilized, computed tomography (CT) has been superseded by magnetic resonance imaging (MRI) for the volumetric assessment of white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF) in the aging human brain. Nevertheless, many scenarios remain where MRI is unavailable or discouraged; furthermore, in developing countries, CT can often be the only accessible imaging method for assessing brain structure in older patients with mild cognitive impairment or Alzheimer’s disease. Thus, there is merit in developing effective approaches for the estimation of brain volumetrics using CT. Here, MRI and CT scans were acquired from 10 older adults [mean (µ) ± standard deviation (σ) of age = 65 ± 7 yrs; 5 females]. To demarcate WM, GM and CSF from head CT, we developed a brain segmentation method based upon probabilistic, atlas-dependent classification. MRI-only segmentation was compared to CT-only segmentation; similarity was calculated through the Dice coefficient (DC). A normal distribution of DCs was found after contrasting the methods [µ ± σ across participants: 85.5% ± 4.6% (WM), 86.7% ± 5.6% (GM) and 91.3% ± 2.8% (CSF)], suggesting a satisfactory capacity of CT to assess brain volumetrics. Sensitivity was adequate: WM, GM and CSF volumes were estimated within ~5%, ~4% and ~3% of their MRI-based values. There was no indication of volume over- or under-estimation with CT [t (9) = 0.89, p > 0.80]. These results facilitate the integration of CT-based brain volumetrics with MRI, thereby offering a wider range of methods for quantifying macroscale brain changes in neurodegenerative diseases.

Retinal degeneration is associated with brain volume reduction and prognosis in radiologically isolated syndrome

Background: The extent of neurodegeneration in the earliest stages of central nervous system (CNS) demyelination is not known. Optical coherence tomography (OCT) is a powerful tool to study neurodegeneration in demyelinating disorders. Objectives: To study neuroaxonal loss in the retina of individuals with radiologically isolated syndrome (RIS) and investigate whether OCT measurements are associated with brain volumetrics and clinical conversion to multiple sclerosis (MS). Methods: Subjects fulfilling the Okuda criteria for RIS ( n = 15 patients, 30 eyes) and age- and sex-matched healthy controls (HC) underwent spectral-domain OCT and magnetic resonance imaging for volumetric measurement of brain structures. Results: Macular ganglion cell-inner plexiform layer (mGCIPL), macular retinal nerve fiber layer (mRNFL), and temporal peripapillary RNFL (pRNFL) thickness; normalized total brain volume (nTBV); and normalized thalamic volume (nTV) were reduced in RIS compared to HC. mGCIPL, mRNFL, and pRNFL measurements were associated with nTBV, nTV, and normalized gray and white matter volumes in the RIS group. pRNFL was thinner in individuals with RIS who converted to MS in 5 years. Conclusions: Retinal neurodegeneration can be detected in the papillomacular region in the earliest stages of CNS demyelination and reflects global disease processes in the brain. OCT can be potentially useful for predicting prognosis in RIS.