Determination of Acrolein-Associated T1 and T2 Relaxation Times and Noninvasive Detection Using Nuclear Magnetic Resonance and Magnetic Resonance Spectroscopy
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An estimated 3.3 million people are living with a traumatic brain injury (TBI)-associated morbidity. Currently, only invasive and sacrificial methods exist to study neurochemical alterations following TBI. Nuclear magnetic resonance methods—magnetic resonance imaging (MRI) and spectroscopy (MRS)—are powerful tools which may be used noninvasively to diagnose a range of medical issues. These methods can be utilized to explore brain functionality, connectivity, and biochemistry. Unfortunately, many of the commonly studied brain metabolites (e.g., N-acetyl-aspartate, choline, creatine) remain relatively stable following mild to moderate TBI and may not be suitable for longitudinal assessment of injury severity and location. Therefore, a critical need exists to investigate alternative biomarkers of TBI, such as acrolein. Acrolein is a byproduct of lipid peroxidation and accumulates following damage to neuronal tissue. Acrolein has been shown to increase in post-mortem rat brain tissue following TBI. However, no methods exist to noninvasively quantify acrolein in vivo. Currently, we have characterized the T1 and T2 of acrolein via nuclear magnetic resonance saturation recovery and Carr–Purcell–Meiboom–Gill experiments, accordingly, to maximize the signal-to-noise ratio of acrolein obtained with MRS. In addition, we have quantified acrolein in water and whole-brain phantom using PRESS MRS and standard post-processing methods. With this potential novel biomarker for assessing TBI, we can investigate methods for predicting acute and chronic neurological dysfunction in humans and animal models. By quantifying and localizing acrolein with MRS, and investigating neurological outcomes associated with in vivo measures, patient-specific interventions could be developed to decrease TBI-associated morbidity and improve quality of life.
This work was supported in part by the National Institutes of Health (Grant Nos. NS073636 and 1 R21 NS090244-01 to R.S.) and a Project Development Team within the ICTSI NIH/NCRR (Grant Number UL1TR001108). The authors gratefully acknowledge support from the Purdue University Center for Cancer Research, NIH grant P30 CA023168. We would also like to acknowledge the Purdue NMR Facility, including Dr. Huaping Mo and Dr. John Harwood, for their expert guidance with experimental design and implementation, and Dr. Gregory Tamer for continued assistance with the 7T Bruker system.
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Conflict of Interest
The authors have no conflicts of interest to declare.
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