In vivo multinuclear magnetic resonance spectroscopy investigations of cerebral development and metabolic encephalopathy using neonatal animal models.

This review has attempted to indicate areas of investigation that in vivo MRS methodology is particularly suited for and would answer important questions related to neonatal cerebral development or injury. There are several metabolites (PEth, PCr, NAA, taurine, glutamate) and lipids detectable by in vivo 31P or 1H MRS, which show substantial changes in concentration during ontogenesis. Do these biochemical markers correlate with major morphological changes, such as myelination? If they do, can this be used to quantitate abnormalities in brain development from congenital abnormalities or metabolic encephalopathies? In the neutral to mild acidic range (7.0 greater than pHi greater than 6.5) adult and neonatal brain appear to have similar intrinsic physicochemical buffering capacity. However, at the extremes of pHi induced by respiratory alkalosis or severe acidosis from partial ischemia, the possibility exists that the buffering capacities of adult and neonatal brain differ. Whether this is true requires further investigations using both neonates and adults, or perhaps more preferably, multiple measurements on a single species throughout its developmental period. Such studies are now feasible because multinuclear in vivo MRS can provide a large body of information from individual animals. A similar study design could prove useful for investigations of changes in cerebral resistance to hypoxia, ischemia, or asphyxia during development. The roles that blood pressure, glucose, temperature, or the administration of extrinsic buffers and drugs have on modulating the severity of and relationship between changes in blood flow, energy metabolites, or pHi, are all amenable to study using in vivo MRS. Furthermore, all of these variables can be measured simultaneously. The kinetics of brain acid and lactate homeostasis during chronic cerebral insults or following acute insults has not been thoroughly examined in either neonates or adult animals. There is evidence to suggest that following ischemia or seizures, brain acidosis resolves before brain lactosis. However, the clinical diagnostic significance of this post-insult uncoupling between pHi and lactate remains to be established. Finally, the application of in vivo MRS methodology to study the effects of trauma, drugs, environmental toxins, and other metabolic encephalopathies on neonatal cerebral perfusion and metabolism are virtually unexplored. Hopefully, the material presented here will prompt researchers to consider the application of in vivo MRS to new avenues of investigation.