pH-weighted molecular MRI in human traumatic brain injury (TBI) using amine proton chemical exchange saturation transfer echoplanar imaging (CEST EPI)

Abstract

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTR asym at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam ( R 2 = 0.4777, P = 0.0021 ), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury ( R 2 = 0.5334, P = 0.0107 ), and a non-linear correlation with the time from injury to MRI exam ( R 2 = 0.6317, P = 0.0004 ). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.

Whole brain snapshot CEST at 3T using 3D‐EPI: Aiming for speed, volume, and homogeneity

“…A previous approach of Zhu et al 25 at 3T enabled a FOV = 212 × 212 × 132 mm 3 at (2.2 mm) 2 in‐plane resolution in 20 s per presaturation offset. A more recent 2D‐EPI–based study of Ellingson et al 26 reported (2 mm) 2 in‐plane resolution with FOV = 256 × 256 × 100 mm 3 in approximately 14 s per presaturation offset, also at B 0 = 3T. Krishnamoorthy et al 27 had chosen a FLASH approach with two shots per readout volume at B 0 = 7T.…”

Proton extrusion during oxidative burst in microglia exacerbates pathological acidosis following traumatic brain injury

“…Clinical studies have shown that brain acidosis severity is a strong predictor of long-term functional outcome (Clausen et al, 2005;Ellingson et al, 2019). To that end, we performed a battery of behavioral tests and histopathological examination to determine the chronic impact of acute brain acidosis on recovery (see Figure S4).…”

“…Although brain tissue acidosis has long been recognized as an important pathological feature of TBI, little is known regarding the cellular and molecular mechanisms involved. Based upon correlational clinical studies, lactic acidosis was implicated as a key mechanism, as brain lactate concentrations are inversely correlated with brain pH after head injury and appear to reliably predict both short-term and long-term clinical outcomes (Clausen et al, 2005;Ellingson et al, 2019;Gupta et al, 2004;Rehncrona, 1985). But the current understanding of TBI-induced acidosis and its underlying mechanisms is limited.…”

Imaging biomarkers of posttraumatic epileptogenesis

“…As rapidly emerging technologies, including new imaging sequences and higher resolution scanners, allow for new visualizations, imaging biomarkers are increasingly promising. 98 Patients with TBI often face prolonged emergency room visits and are particularly susceptible to motion artifacts that may render images unreadable. More advanced diffusion MRI techniques that use multishell sampling and biophysical modeling can separate these features.…”

“…These methods include susceptibility-weighted imaging and derived quantitative susceptibility mapping that have been utilized to characterize diffuse axonal injury and identify chronic hemosiderosis better than existing sequences 96 ; magnetic transfer ratio imaging, which has been shown to decrease in association with axonal injury 97 ; and chemical exchange saturation transfer echoplanar imaging, which was recently shown to successfully identify tissue at risk for chronic injury due to cerebral acidosis in a clinical setting. 98 Patients with TBI often face prolonged emergency room visits and are particularly susceptible to motion artifacts that may render images unreadable. New preprocessing tools may compensate for this loss of data.…”