Brain Changes to Hypocapnia Using Rapidly Interleaved Phosphorus-Proton Magnetic Resonance Spectroscopy at 4 T

Abstract

Substantial controversy persists in the literature concerning the physiologic consequences hypocapnia, or low partial pressure of carbon dioxide (PaCO 2 ). Invasive animal studies have demonstrated large pH increases ( > 0.25 U), phosphocreatine (PCr) decreases ( > 30%), and adenosine triphosphate (ATP) decreases ( > 10%) after hyperventilation (HV) (20 mm Hg PaCO 2 ). However, using magnetic resonance spectroscopy, HV studies in awake humans have demonstrated only small pH changes (B0.05 U) and no changes in PCr or ATP. It remains important to ascertain whether this failure to detect PCr changes in human studies reflects a true absence of changes, or a limitation in data fidelity. The present study used a rapidly interleaved phosphorus-proton spectroscopy acquisition from large samples at high magnetic field (4 T), to measure pH, PCr, inorganic phosphate, b-ATP, and lactate changes with high temporal and signal sensitivity. Five of six subjects had usable data. During 20 mins HV, PaCO 2 reached a minimum at 16 mins (17 mm Hg); however, the maximum pH change ( + 0.047) peaked earlier (14 mins). Maximal lactate increases were measured at 15 mins. By 10 mins, maximum changes were observed for PCr (À3.4%) and inorganic phosphate ( + 6.4%). No changes in b-ATP were observed. The peak in pH, despite continued decreases in PaCO 2 , suggests active buffering during HV. These data, and the small magnitude of early PCr and inorganic phosphate changes, do not support substantial energy compromise during HV. Other mitigating factors, such as anesthesia-induced deregulation of the cerebrovasculature, might have contributed to the exaggerated metabolic changes observed in previous animal investigations.

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

“…This consideration does highlight that although 1 H MRS provides sensitive measurement of lactate levels localized to the brain, lactate elevations are not specific to mitochondrial dysfunction and can result from acute physiological alterations, such as hyperventilation (Dager et al 1995;Friedman et al 2007;Posse et al 1997) or following caffeine ingestion (Dager et al 1999). In this study, the use of propofol sedation allowed us to image the children with ASD and DD at rest, which minimized the effects of emotional or stress-driven physiological changes on lactate levels in these groups.…”

“…To date, there have been no additional published 31 P MRS studies of ASD to follow-up on that initial report. More recent work using 31 P MRS to measure brain pH shifts associated with metabolic alterations (Friedman et al 2006b) and rapidly interleaved 31 P-1 H MRS techniques at high-field to characterize the effects of hypocapneainduced lactate changes on high-energy phosphates (Friedman et al 2007) suggest that 31 P MRS has the potential to broaden clinical investigations of brain bioenergetic status in ASD. However, the specificity and sensitivity of 31 P MRS for detecting high-energy phosphate alterations associated with mitochondrial dysfunction, as well the range of normal values in the absence of mitochondrial dysfunction, requires further assessment.…”

Changes in visual-evoked potential habituation induced by hyperventilation in migraine

“…If their firing rate decreases during HV then decreased firing might further aggravate their hypofunction in migraineurs and worsen the thalamocortical dysrhythmia. Here, whether the known persistent increase in lactate levels induced by HV [2, 4, 48] plays a role in the VEP changes remains to be determined. Collectively the above-mentioned findings seem to support our earlier hypothesis that the interictal habituation deficit in migraine reflects reduced thalamocortical drive and hence a low preactivation level of sensory cortices [21, 22].…”

“…Stress is often associated with hyperventilation (HV). HV induces several physiological changes in the human central nervous system and does so by altering eucarbia, local cerebral blood flow, brain tissue oxygenation, pH and lactate [2–5]. For instance, HV slows the electroencephalogram (EEG) by increasing delta-power and decreasing alpha-power [6, 7].…”

Improving 1H MRSI measurement of cerebral lactate for clinical applications

“…Lactate exists in the healthy brain at low basal concentrations, and elevations can indicate transient changes in physiological state (van Rijen et al, 1989; Dager et al, 1999b; Friedman et al, 2007) or neural activation (Prichard et al, 1991; Sappey-Marinier et al, 1992; Frahm et al, 1996), as well as altered metabolic regulation such as in bipolar disorder (Dager et al, 2004) and panic disorder (Dager et al, 1994; Maddock, 2001). Other brain pathological states also exhibit characteristic brain lactate elevations, including tumors (Sijens et al, 1996), ischemia (Behar et al, 1983; Mathews et al, 1995), traumatic brain injury (Makoroff et al, 2005), and metabolic compromise from severe mitochondrial dysfunction, such as in MELAS (Kaufmann et al, 2004) or Leigh syndrome (Sijens et al, 2008).…”