Cerebral Diffusion and T₂: MRI Predictors of Acute Mountain Sickness during Sustained High-Altitude Hypoxia

Abstract

Diffusion magnetic resonance imaging (MRI) provides a sensitive indicator of cerebral hypoxia. We investigated if apparent diffusion coefficient (ADC) and transverse relaxation (T 2 ) predict symptoms of acute mountain sickness (AMS), or merely indicate the AMS phenotype irrespective of symptoms. Fourteen normal subjects were studied in two groups; unambiguous AMS and no-AMS at 3,800 m altitude (intermediate AMS scores were excluded). T 2 relaxation was estimated from a T 2 index of T 2 -weighted signal normalized by cerebrospinal fluid signal. Measurements were made in normoxia and repeated after 2 days sustained hypoxia (AMS group symptomatic and no-AMS group asymptomatic) and after 7 days hypoxia (both groups asymptomatic). Decreased ADC directly predicted AMS symptoms (Po0.05). Apparent diffusion coefficient increased in asymptomatic subjects, or as symptoms abated with acclimatization. This pattern was similar in basal ganglia, white matter, and gray matter. Corpus callosum behaved differently; restricted diffusion was absent (or rapidly reversed) in the splenium, and was sustained in the genu. In symptomatic subjects, T 2,index decreased after 2 days hypoxia and further decreased after 7 days. In asymptomatic subjects, T 2,index initially increased after 2 days, but decreased after 7 days. T 2,index changes were not predictive of AMS symptoms. These findings indicate that restricted diffusion, an indicator of diminished cerebral energy status, directly predicts symptoms of AMS in humans at altitude.

Investigation of Whole-Brain White Matter Identifies Altered Water Mobility in the Pathogenesis of High-Altitude Headache

“…Although contradictory to the conventional hypothesis, our findings of focally reduced brain water during acute normobaric hypoxia do agree with the recent findings of reduced T 2 -weighted signal intensity during prolonged residence (7 days) at terrestrial altitude. 8 Using a combination of TBSS and ROI analyses, we identified that 2 hours in hypoxia caused a focal reduction in mean diffusivity within the posterior left hemisphere (TBSS) that propagated throughout cerebral white matter by 10 hours (using both TBSS and skeletonized regions of interest). After both 2 and 10 hours in hypoxia, concomitant increases in fractional anisotropy were also observed using a region of interest analysis.…”

“…Subsequently, we explored the relationship between the development of a specific acute mountain sickness symptom, headache, with changes in brain water mobility and content after 2 hours (presymptomatic) and 10 hours (symptomatic) in hypoxia. Given the lack of molecular evidence for breakdown of the bloodbrain barrier in hypoxia, 10,11 but evidence for the accumulation of both extracellular and intracellular water, 3,4,8 we hypothesized that early hypoxia (2 hours) will be characterized by a reduction in mean diffusivity and increased fractional anisotropy but no change in T 2 in line with a fluid shift into the intracellular space. In contrast, more prolonged hypoxia (10 hours) will be associated with reduced mean diffusivity but increased fractional anisotropy and T 2 , which would suggest an increase in brain edema.…”

Long‐term acclimatization to high‐altitude hypoxia modifies interhemispheric functional and structural connectivity in the adult brain

“…2012, 2013; Hunt et al. 2013). Furthermore, increases in FA values in the corticospinal tract and CC were only found in HA immigrant descendants (Zhang et al.…”

Cerebral Volumetric Changes Induced by Prolonged Hypoxic Exposure and Whole-Body Exercise

“…A reduction in ADC is generally Hypoxia, exercise, and cerebral volume T Rupp et al interpreted as a consequence of cytotoxic edema with intracellular swelling and may be associated with perturbations in cellular energy status responsible for reduced Na + /K + ATPase pump and altered ionic homeostasis. 9,25 Previous studies regarding the effect of hypoxic exposure on ADC reported contradictory results with increased 3,4,14 or reduced 5,10 ADC values. Hunt et al 9 reported significant reduction in ADC values among subjects with AMS after 48 hours at 3,800 m while ADC was increased in subjects without AMS.…”

“…The absence of correlation between symptoms of AMS and changes in brain volume or ADC during 10 hours of hypoxic exposure cannot exclude any consequences of cerebral changes over longer hypoxic exposure duration where symptoms are known to be the most severe (12 to 48 hours). 9 …”