Phosphorous magnetic resonance spectroscopy (31P-MRS) is suited to noninvasively investigate energy metabolism and to detect molecules containing phosphorus in the human brain. The aim of this longitudinal study was to perform 31P-MRS at two different time points (within 72 h and between day 10–14) after severe traumatic brain injury (sTBI) to reveal alterations in cerebral energy metabolism. Twenty-six ventilated patients with sTBI, aged between 20 and 75 years, with a median initial Glasgow Coma Scale score of 5 were analyzed prospectively. The 31P-MRS data of the structurally more affected side were compared with data from contralateral normal appearing areas and with data of age- and gender-matched healthy controls. There were no significant intraindividual differences between the lesioned and the less affected side at either of the time points. In the acute phase, phosphocreatine/adenosine triphosphate (PCr/ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) were significantly elevated whereas phosphomonoesters/phosphodiesters (PME/PDE) and Pi/ATP were significantly decreased in contrast to healthy controls. In the subacute phase, these differences gradually dissipated, remaining lower Pi/ATP ratio, and only partly altered levels of PCr/Pi and PME/PDE. Our data affirm that cerebral metabolism is globally altered after sTBI, demonstrating the diffuse impairment of brain bioenergetics at multiple levels, with resultant developments in terms of time.
Get full access to this article
View all access options for this article.
References
1.
PinggeraD., SteigerR., BauerM., KerschbaumerJ., LugerM., BeerR., RietzlerA., GramsA.E., GizewskiE.R., ThomeC., and PetrO. (2021). Cerebral energy status and altered metabolism in early severe TBI: first results of a prospective (31)P-MRS feasibility study. Neurocrit. Care, 34, 432–440.
2.
PinggeraD., LugerM., BürglerI., BauerM., ThoméC., and PetrO. (2020). Safety of early MRI examinations in severe TBI: a test battery for proper patient selection. Front. Neurol. 11, 219.
3.
CarneyN., TottenA.M., O'ReillyC., UllmanJ.S., HawrylukG.W., BellM.J., BrattonS.L., ChesnutR., HarrisO.A., KissoonN., RubianoA.M., ShutterL., TaskerR.C., VavilalaM.S., WilbergerJ., WrightD.W., and GhajarJ. (2017). Guidelines for the management of severe traumatic brain injury, Fourth Edition. Neurosurgery, 80, 6–15.
4.
HattingenE., MagerkurthJ., PilatusU., MozerA., SeifriedC., SteinmetzH., ZanellaF., and HilkerR. (2009). Phosphorus and proton magnetic resonance spectroscopy demonstrates mitochondrial dysfunction in early and advanced Parkinson's disease. Brain, 132, 3285–3297.
5.
HattingenE., LanfermannH., QuickJ., FranzK., ZanellaF.E., and PilatusU. (2009). 1H MR spectroscopic imaging with short and long echo time to discriminate glycine in glial tumours. MAGMA, 22, 33–41.
6.
SteigerR., WalchhoferL.M., RietzlerA., MairK.J., KnoflachM., GlodnyB., GizewskiE.R., and GramsA.E. (2018). Cerebral phosphorus magnetic resonance spectroscopy in a patient with giant cell arteritis and endovascular therapy. Case Rep. Radiol. 2018, 7806395.
7.
VanhammeL., van den BoogaartA., and Van HuffelS. (1997). Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J. Magn. Reson. 129, 35–43.
8.
LiuY., GuY., and YuX. (2017). Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review. Quant. Imaging Med. Surg. 7, 707–726.
9.
BeerM., SeyfarthT., SandstedeJ., LandschützW., LipkeC., KöstlerH., von KienlinM., HarreK., HahnD., and NeubauerS. (2002). Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with 31P-SLOOP magnetic resonance spectroscopy. J. Am. Coll. Cardiol. 40, 1267–1274.
10.
KempG.J. (2000). Non-invasive methods for studying brain energy metabolism: what they show and what it means. Dev. Neurosci. 22, 418–428.
11.
ChanceB., ImJ., NiokaS. and KushmerickM. (2006). Skeletal muscle energetics with PNMR: personal views and historic perspectives. NMR Biomed. 19, 904–926.
12.
DalyJ.J. (1987). Phospholipid Metabolism in Cancer Cells monitored by 31PMRS.
13.
ShiX.F., CarlsonP.J., SungY.H., FiedlerK.K., ForrestL.N., HellemT.L., HuberR.S., KimS.E., ZuoC., JeongE.K., RenshawP.F., and KondoD.G. (2015). Decreased brain PME/PDE ratio in bipolar disorder: a preliminary (31) P magnetic resonance spectroscopy study. Bipolar Disord. 17, 743–752.
14.
KreisR. (2004). Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a gallery of artifacts. NMR Biomed. 17, 361–381.
15.
NgS.Y., and LeeA.Y.W. (2019). Traumatic brain injuries: pathophysiology and potential therapeutic targets. Front. Cell. Neurosci, 13, 528.
16.
StovellM.G., MadaM.O., CarpenterT.A., YanJ.L., GuilfoyleM.R., JallohI., WelshK.E., HelmyA., HoweD.J., GriceP., MasonA., Giorgi-CollS., GallagherC.N., MurphyM.P., MenonD.K., HutchinsonP.J., and CarpenterK.L. (2018). Phosphorus spectroscopy in acute TBI demonstrates metabolic changes that relate to outcome in the presence of normal structural MRI. J. Cereb. Blood Flow Metab. 40, 67–84.
17.
GarnettM.R., CorkillR.G., BlamireA.M., RajagopalanB., MannersD.N., YoungJ.D., StylesP., and Cadoux-HudsonT.A. (2001). Altered cellular metabolism following traumatic brain injury: a magnetic resonance spectroscopy study. J. Neurotrauma, 18, 231–240.
18.
VinkR., FadenA.I., and McIntoshT.K. (1988). Changes in cellular bioenergetic state following graded traumatic brain injury in rats: determination by phosphorus 31 magnetic resonance spectroscopy. J. Neurotrauma, 5, 315–330.
19.
VinkR., McIntoshT.K., WeinerM.W., and FadenA.I. (1987). Effects of traumatic brain injury on cerebral high-energy phosphates and pH: a 31P magnetic resonance spectroscopy study. J. Cereb. Blood Flow Metab. 7, 563–571.
20.
IshigeN., PittsL.H., BerryI., NishimuraM.C., and JamesT.L. (1988). The effects of hypovolemic hypotension on high-energy phosphate metabolism of traumatized brain in rats. J. Neurosurg. 68, 129–136.
21.
Di PietroV., AmoriniA.M., TavazziB., VagnozziR., LoganA., LazzarinoG., SignorettiS., LazzarinoG., and BelliA. (2014). The molecular mechanisms affecting N-acetylaspartate homeostasis following experimental graded traumatic brain injury. Mol. Med. 20, 147–157.
22.
SignorettiS., VagnozziR., TavazziB., and LazzarinoG. (2010). Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications. Neurosurg. Focus, 29, E1.
23.
SmithD.H., CecilK.M., MeaneyD.F., ChenX.H., McIntoshT.K., GennarelliT.A., and LenkinskiR.E. (1998). Magnetic resonance spectroscopy of diffuse brain trauma in the pig. J. Neurotrauma, 15, 665–674.
24.
UnterbergA.W., AndersenB.J., ClarkeG.D., and MarmarouA. (1988). Cerebral energy metabolism following fluid-percussion brain injury in cats. J. Neurosurg. 68, 594–600.
25.
SignorettiS., Di PietroV., VagnozziR., LazzarinoG., AmoriniA.M., BelliA., D'UrsoS., and TavazziB. (2010). Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat. Mol. Cell. Biochem. 333, 269–277.
26.
AgostonD.V., VinkR., HelmyA., RislingM., NelsonD., and PrinsM. (2019). How to translate time: the temporal aspects of rodent and human pathobiological processes in traumatic brain injury. J. Neurotrauma, 36, 1724–1737.
27.
BoltonA.N., and SaatmanK.E. (2014). Regional neurodegeneration and gliosis are amplified by mild traumatic brain injury repeated at 24-hour intervals. J. Neuropathol. Exp. Neurol. 73, 933–947.
28.
FehilyB., and FitzgeraldM. (2017). Repeated mild traumatic brain injury: potential mechanisms of damage. Cell Transplant, 26, 1131–1155.
29.
KambleR.B., PeruvumbaN.J., and ShivashankarR. (2014). Energy status and metabolism in intracranial space occupying lesions: a prospective 31p spectroscopic study. J. Clin. Diagn. Res. 8, RC05–RC08.
30.
SteenC., WilczakN., HoogduinJ.M., KochM., and De KeyserJ. (2010). Reduced creatine kinase B activity in multiple sclerosis normal appearing white matter. PloS One, 5, e10811.
31.
BramlettH.M,. and DietrichW.D. (2015). Long-term consequences of traumatic brain injury: current status of potential mechanisms of injury and neurological outcomes. J. Neurotrauma, 32, 1834–1848.
32.
BellanderB.M., LidmanO., OhlssonM., MeijerB., PiehlF., and SvenssonM. (2010). Genetic regulation of microglia activation, complement expression, and neurodegeneration in a rat model of traumatic brain injury. Exp. Brain Res. 205, 103–114.
33.
CunninghamA.S., SalvadorR., ColesJ.P., ChatfieldD.A., BradleyP.G., JohnstonA.J., SteinerL.A., FryerT.D., AigbirhioF.I., SmielewskiP., WilliamsG.B., CarpenterT.A., GillardJ.H., PickardJ.D., and MenonD.K. (2005). Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury. Brain, 128, 1931–1942.
34.
StovellM.G., YanJ.L., SleighA., MadaM.O., CarpenterT.A., HutchinsonP.J., and CarpenterK.L.H. (2017). Assessing metabolism and injury in acute human traumatic brain injury with magnetic resonance spectroscopy: current and future applications. Front. Neurol. 8, 426.
35.
ChengG., FuL., ZhangH.Y., WangY.M., ZhangL.M., and ZhangJ.N. (2013). The role of mitochondrial calcium uniporter in neuroprotection in traumatic brain injury. Med. Hypotheses, 80, 115–117.
36.
CarpenterK.L., CzosnykaM., JallohI., NewcombeV.F., HelmyA., ShannonR.J., BudohoskiK.P., KoliasA.G., KirkpatrickP.J., CarpenterT.A., MenonD.K., and HutchinsonP.J. (2015). Systemic, local, and imaging biomarkers of brain injury: more needed, and better use of those already established?. Front. Neurol. 6, 26.
37.
TimofeevI., CarpenterK.L., NortjeJ., Al-RawiP.G., O'ConnellM.T., CzosnykaM., SmielewskiP., PickardJ.D., MenonD.K., KirkpatrickP.J., GuptaA.K., and HutchinsonP.J. (2011). Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain, 134, 484–494.
38.
Cadoux-HudsonT.A., WadeD., TaylorD.J., RajagopalanB., LedinghamJ.G., BriggsM., and RaddaG.K. (1990). Persistent metabolic sequelae of severe head injury in humans in vivo. Acta Neurochir. 104, 1–7.
39.
LanganC., and McDonaldC. (2009). Neurobiological trait abnormalities in bipolar disorder. Mol. Psychiatry, 14, 833–846.
40.
ZaninottoA.L., VicentiniJ.E., FregniF., RodriguesP.A., BotelhoC., de LuciaM.C,. and PaivaW.S. (2016). Updates and current perspectives of psychiatric assessments after traumatic brain injury: a systematic review. Front. Psychiatry, 7, 95.
41.
PerryD.C., SturmV.E., PetersonM.J., PieperC.F., BullockT., BoeveB.F., MillerB.L., GuskiewiczK.M., BergerM.S., KramerJ.H., and Welsh-BohmerK.A. (2016). Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis. J. Neurosurg. 124, 511–526.
42.
ZgaljardicD.J., SealeG.S., SchaeferL.A., TempleR.O., ForemanJ., and ElliottT.R. (2015). Psychiatric disease and post-acute traumatic brain injury. J. Neurotrauma, 32, 1911–1925.
43.
McKeeA.C., and DaneshvarD.H. (2015). The neuropathology of traumatic brain injury. Handb. Clin. Neurol. 127, 45–66.
44.
BelangerH.G., VanderploegR.D., CurtissG., and WardenD.L. (2007). Recent neuroimaging techniques in mild traumatic brain injury. J. Neuropsychiatry Clin. Neurosci. 19, 5–20.
45.
KurcaE., SivakS., and KuceraP. (2006). Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging. Neuroradiology, 48, 661–669.
46.
BenderM., SteinM., KimS.W., UhlE., and SchollerK. (2021). Serum biomarkers for risk assessment of intrahospital transports in mechanically ventilated neurosurgical intensive care unit patients. J. Intensive Care Med. 36, 419–427.
47.
VeigaV.C., PostalliN.F., AlvarisaT.K., TravassosP.P., ValeR., OliveiraC.Z., and RojasS.S. (2019). Adverse events during intrahospital transport of critically ill patients in a large hospital. Rev. Bras. Ter. Intensiva, 31, 15–20.
48.
NilssonL., and SiesjoB.K. (1974). Influence of anaesthetics on the balance between production and utilization of energy in the brain. J. Neurochem. 23, 29–36.
