RESUMO
BACKGROUND: To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. METHODS: We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5 T or 3 T. Healthy controls were investigated with both 1.5 T and 3 T ASL-MRI. RESULTS: We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56 years, range 18-82 years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50 years, range 21-77 years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2 mL/100 g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CONCLUSIONS: CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.
RESUMO
The aim of this study was to quantify the total number of neurons and glial cells in the mediodorsal nucleus of the thalamus (MD) of 8 newborn human brains, in comparison to 8 adult human brains. The estimates of the cell numbers were obtained using the stereological principles of the optical fractionator. In the case of the adults, the total number of neurons in the entire MD was an average of 41% lower than in the newborn, which was statistically highly significant (P < 0.001). The estimated average total number of neurons in MD thalamus of the newborns was 11.2 million (coefficient of variation [CV] = standard deviation/mean = 0.16), compared with the adults' 6.43 million (CV = 0.15). The glial cell numbers were substantially higher in the adult brains, with an increase of almost 4 times from 10.6 million at birth to 36.3 million in the fully developed adult brain. This is the first demonstration of a higher number of human neurons in the brain of newborns compared with the adult.