Search

Purpose: To assess the feasibility of CEST‐based creatine (Cr) mapping in brain at 3T using the guanidino (Guan) proton resonance. Methods: Wild type and knockout mice with guanidinoacetate N‐methyltransferase deficiency and low Cr and phosphocreatine (PCr) concentrations in the brain were used to assign the Cr and protein‐based arginine contributions to the GuanCEST signal at 2.0 ppm. To quantify the Cr proton exchange rate, two‐step Bloch–McConnell fitting was used to fit the extracted CrCEST line‐shape and multi‐B1 Z‐spectral data. The pH response of GuanCEST was simulated to demonstrate its potential for pH mapping. Results: Brain Z‐spectra of wild type and guanidinoacetate N‐methyltransferase deficiency mice show a clear Guan proton peak at 2.0 ppm at 3T. The CrCEST signal contributes ∼23% to the GuanCEST signal at B1 = 0.8 μT, where a maximum CrCEST effect of 0.007 was detected. An exchange rate range of 200–300 s−1 was estimated for the Cr Guan protons. As revealed by the simulation, an elevated GuanCEST in the brain is observed when B1 is less than 0.4 μT at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B1 is greater than 0.4 μT with the same pH drop. Conclusions: CrCEST mapping is possible at 3T, which has potential for detecting intracellular pH and Cr concentration in brain. [ABSTRACT FROM AUTHOR]

Cerebral venous oxygenation (Yv) is a valuable biomarker for a variety of brain diseases. T2 relaxation under spin tagging (TRUST) MRI is a widely used method for Yv quantification. In this work, there were two main objectives. The first was to evaluate the reproducibility of TRUST Yv measurements across MRI scanners from different vendors. The second was to examine the correlation between Yv and end‐tidal CO2 (EtCO2) in a multisite, multivendor setting and determine the usefulness of this correlation to account for variations in Yv caused by normal variations and physiological fluctuations. Standardized TRUST pulse sequences were implemented on three scanners from major MRI vendors (GE, Siemens, Philips). These scanners were located at two research institutions. Ten healthy subjects were scanned. On each scanner, the subject underwent two scan sessions, each of which included three TRUST scans, to evaluate the intrasession and intersession reproducibility of Yv. Each scanner was also equipped with a capnograph device to record the EtCO2 of the subject during the MRI scan. We found no significant bias in Yv measurements across the three scanners (P = 0.18). The measured Yv values on the three scanners were also strongly correlated with each other (intraclass correlation coefficients > 0.85, P < 0.001). The intrasession and intersession coefficients of variation of Yv were less than 4% and showed no significant difference among the scanners. In addition, our results revealed that (1) within the same subject, Yv increased with EtCO2 at a rate of 1.24 ± 0.17%/mmHg (P < 0.0001), and (2) across different subjects, individuals with a higher EtCO2 had a higher Yv, at a rate of 0.94 ± 0.36%/mmHg (P = 0.01). These results suggest that (1) the standardized TRUST sequences had similar accuracies and reproducibilities for the quantification of Yv across the scanners, and (2) recording of EtCO2 may be a useful complement to Yv measurement to account for CO2‐related physiological fluctuations in Yv in multisite, multivendor studies. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma neurofilament light chain (NfL) is associated with dementia, but the specific underlying mechanisms are largely unknown. We examined cross‐sectional and longitudinal relationships of plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia, namely global and cortical brain, hippocampal and white matter lesion volumes (WMLV). Method: Data were extracted from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004‐2009) and v2 (2009‐2013) plasma NfL exposure and ancillary sMRI data at vscan (2011‐2015, n = 179, mean v1 to vscan time: 5.4y). Multivariable‐adjusted linear regression models were conducted, overall, by sex, and by race, correcting for multiple testing with q‐values. Result: NfL(v1) (Loge transformed) had a moderately strong association with larger WMLV at follow‐up vscan visit, after a period of 5‐6 years of follow‐up, overall (β = +2.131±0.660, b = +0.29, p = 0.001, q = 0.0029). Moreover, a 1 unit increase in NfLv2 was linked to a left hippocampal volume that was lower by 125 mm3 (p = 0.004, q = 0.015), using minimally adjusted models and mainly among males. Associations were largely unaltered by further adjustment for downstream health‐related factors. Conclusion: In summary, plasma NfL may be an independent medium‐term (within 5 years) marker for increase in WMLV, and a short term (within 1 year) marker for smaller hippocampal volumes normalized to the intracranial volume, independently of other confounding factors. Therefore, plasma NfL holds promise as a blood‐based marker to predict future subclinical brain pathologies in middle‐aged adults. [ABSTRACT FROM AUTHOR]