Rapid simultaneous estimation of relaxation rates using multi-echo, multi-contrast MRI.

PURPOSE: Multi-echo, multi-contrast methods are increasingly used in dynamic imaging studies to simultaneously quantify R2∗ and R2. To overcome the computational challenges associated with nonlinear least squares (NLSQ) fitting, we propose a generalized linear least squares (LLSQ) solution to rapidly fit R2∗ and R2. METHODS: Spin- and gradient-echo (SAGE) data were simulated across T2∗ and T2 values at high (200) and low (20) SNR. Full (four-parameter) and reduced (three-parameter) parameter fits were implemented and compared with both LLSQ and NLSQ fitting. Fit data were compared to ground truth using concordance correlation coefficient (CCC) and coefficient of variation (CV). In vivo SAGE perfusion data were acquired in 20 subjects with relapsing-remitting multiple sclerosis. LLSQ R2∗ and R2, as well as cerebral blood volume (CBV), were compared with the standard NLSQ approach. RESULTS: Across all fitting methods, T2∗ was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.87, CV ≤ 0.08) SNR. Except for short T2∗ values (5-15 ms), T2 was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.99, CV ≤ 0.03) SNR. In vivo, LLSQ R2∗ and R2 estimates were similar to NLSQ, and there were no differences in R2∗ across fitting methods at high SNR. However, there were some differences at low SNR and for R2 at high and low SNR. In vivo NLSQ and LLSQ three parameter fits performed similarly, as did NLSQ and LLSQ four-parameter fits. LLSQ CBV nearly matched the standard NLSQ method for R2∗- (0.97 ratio) and R2-CBV (0.98 ratio). Voxel-wise whole-brain fitting was faster for LLSQ (3-4 min) than NLSQ (16-18 h). CONCLUSIONS: LLSQ reliably fit for R2∗ and R2 in simulated and in vivo data. Use of LLSQ methods reduced the computational demand, enabling rapid estimation of R2∗ and R2.

White Matter Microstructure Analysis in Subjective Memory Complaints and Cognitive Impairment: Insights from Diffusion Kurtosis Imaging and Free-Water DTI.

Background: Dementia is characterized by a cognitive decline in memory and other domains that lead to functional impairments. As people age, subjective memory complaints (SMC) become common, where individuals perceive cognitive decline without objective deficits on assessments. SMC can be an early sign and may precede amnestic mild cognitive impairment (MCI), which frequently advances to Alzheimer's disease (AD). Objective: This study aims to investigate white matter microstructure in individuals with SMC, in cognitively impaired (CI) cohorts, and in cognitively normal individuals using diffusion kurtosis imaging (DKI) and free water imaging (FWI). The study also explores voxel-based correlations between DKI/FWI metrics and cognitive scores to understand the relationship between brain microstructure and cognitive function. Methods: Twelve healthy controls (HCs), ten individuals with SMC, and eleven CI individuals (MCI or AD) were enrolled in this study. All participants underwent MRI 3T scan and the BNI Screen (BNIS) for Higher Cerebral Functions. Results: The mean kurtosis tensor and anisotropy of the kurtosis tensor showed significant differences across the three groups, indicating altered white matter microstructure in CI and SMC individuals. The free water volume fraction (f) also revealed group differences, suggesting changes in extracellular water content. Notably, these metrics effectively discriminated between the CI and HC/SMC groups. Additionally, correlations between imaging metrics and BNIS scores were found for CI and SMC groups. Conclusions: These imaging metrics hold promise in discriminating between individuals with CI and SMC. The observed differences indicate their potential as sensitive and specific biomarkers for early detection and differentiation of cognitive decline.