ABSTRACT Background White matter microstructure may be affected by cancer and its treatment, yet its association with subsequent cancer‐related cognitive impairment (CRCI) remains unclear. Purpose To investigate whether baseline white matter diffusion metrics are associated with the time to CRCI onset and longitudinal cognitive trajectories. Study Type Prospective longitudinal study. Population A total of 230 female patients (49.4 ± 8.6 years) with histopathologically confirmed breast cancer (50 Stage II, 180 Stage III) with planned neoadjuvant chemotherapy before surgery. Field Strength/Sequence A 3 T, multi‐shell SE ‐ EPI DWI . Assessment Diffusion MRI was performed before chemotherapy (baseline). Neuropsychological assessments were carried out at baseline, after the first cycle of chemotherapy, after completion of chemotherapy but before surgery, and at 2–4 years after surgery. Diffusion tensor metrics (mean, radial, and axial diffusivity [MD, RD, and AD]), diffusion kurtosis metrics (axial and radial kurtosis [AK and RK]), and neurite orientation dispersion and density imaging metrics (orientation dispersion index [ODI], neurite density index [NDI]) were extracted from 25 white matter tracts, capturing both mean values and peak width. Statistical Tests Cox regression and linear mixed‐effects models assessed associations with time to CRCI onset and cognitive trajectories, respectively. A p value < 0.05 was considered significant. Results Higher ODI (anterior limb of the internal capsule [ALIC]: HR = 1.28), lower AD (ALIC: HR = 0.72, external capsule [EC]: HR = 0.73, superior fronto‐occipital fasciculus [SFO]: HR = 0.70), and greater peak width of AK (ALIC: HR = 1.29, EC: HR = 1.24, genu of the corpus callosum [GCC]: HR = 1.32) were associated with earlier CRCI onset. Lower FA, RK, and MK ( β = 0.13 to 0.27 × 10 −3 ), higher MD, RD, ODI, and ISOVF ( β = −0.23 to −0.13 × 10 −3 ), and higher peak width metrics ( β = −0.34 to −0.13 × 10 −3 ) were associated with poorer longitudinal cognitive trajectories. Conclusions Pretreatment white matter microstructure may help identify patients at greater risk of CRCI and poorer cognitive trajectories. Level of Evidence 2. Technical Efficacy Stage 3.
ABSTRACT Background Morphometric measurements from structural brain MRI are sensitive to analysis pipelines and software versions. Purpose To evaluate inter‐pipeline agreement, reliability, and systematic measurement differences across automated morphometric software packages on identical structural MRI datasets. Study Type Systematic review (PROSPERO CRD420261456493). Population One hundred eleven studies comprising healthy and clinical cohorts across the lifespan. Field Strength/Sequence Predominantly 1.5 T and 3 T, with 7 T data also included. Assessment Automated and semi‐automated processing pipelines (predominantly FreeSurfer, FSL, and SPM/CAT) evaluated for brain volumes and cortical thickness. Statistical Tests Intraclass correlation coefficients (ICC), Pearson/Spearman correlation (r), Lin's concordance correlation coefficient (CCC), and Bland–Altman bias ( p < 0.05). Results Agreement varied across anatomical regions, software pairs, versions, and processing conditions. Strong associations coexisted with systematic measurement differences in several comparisons, but neither high association nor high agreement was consistent across global and regional outputs. Manual‐reference comparisons showed structure‐ and population‐dependent volume overestimation, with rankings differing by outcome metric. Cortical thickness, intracranial‐volume normalization, and normative percentiles showed additional method‐dependent differences. Software updates and preprocessing choices altered measurements and, in some studies, downstream findings. Computational repeatability, anatomical accuracy, and longitudinal‐change agreement represented distinct properties and did not consistently favor the same method. Data Conclusion High correlation or consistency does not ensure absolute agreement or interchangeability in MRI morphometry. Regional discrepancies vary across software pairs, versions, and processing conditions, limiting generalization of individual comparisons to other methods or populations. Evidence Level 1. Technical Efficacy Stage Stage 2.
ABSTRACT Background Diffusion tensor imaging (DTI) is sensitive to white matter (WM) microstructural alterations in multiple sclerosis (MS), but duration‐defined “early MS” cohorts may be clinically heterogeneous. Purpose To investigate diffusion alterations in WM and normal‐appearing white matter (NAWM) in low‐disability MS versus healthy controls (HC). Study Type Retrospective cross‐sectional case–control study. Population 20 patients with MS (Expanded Disability Status Scale ≤ 3.5; ambulatory without assistance) and 20 age‐ and sex‐matched HC. Sequence 3. 0 T ; 3D T1 ‐weighted and FLAIR sequences and a single‐shot spin‐echo echo‐planar sequence with 60 diffusion directions (b = 1000 s/mm 2 ) and nine b0 volumes. Assessment Tract‐Based Spatial Statistics (TBSS) assessed fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in conventional WM and lesion‐masked NAWM. DeepLesionBrain (volBrain) automatically segmented WM lesions; a neuroradiologist with 10 years of experience reviewed and corrected segmentations when necessary. Statistical Test FMRIB Software Library (FSL) randomize using 10,000 permutations, threshold‐free cluster enhancement, and family‐wise error correction ( p < 0.01). Permutation Analysis of Linear Models (PALM) used two‐sided inference and FWE correction across diffusion metrics and directions. Results Standard TBSS showed lower FA in the right anterior corona radiata (ACR) and posterior thalamic radiation (PTR), and higher RD in the corpus callosum genu, in MS versus HC. NAWM‐restricted TBSS showed lower FA in the corpus callosum genu, right PTR, and right tapetum, and higher RD in bilateral ACR, right posterior corona radiata, and an unclassified region. In randomized, AD and MD were nonsignificant (minimum corrected p = 0.0118 and 0.0103 in standard TBSS; p = 0.0103 and 0.0107 in NAWM, respectively). Under PALM across‐metric correction, no metric remained significant: standard TBSS, FA p = 0.0861, AD p = 0.1273, RD p = 0.0271, MD p = 0.0177; NAWM, FA p = 0.0807, AD p = 0.1225, RD p = 0.0282, MD p = 0.0197. Conclusion Functionally defined low‐disability MS shows focal WM and NAWM microstructural alterations, predominantly reflected by reduced FA and increased RD. Evidence Level 4. Technical Efficacy Stage 1.
Background 13C magnetic resonance spectroscopy (MRS), combined with 13C-labeled substrate infusion, offers a nonionizing, minimally invasive method for assessing fluxes through the main cerebral energy metabolism pathways. However, its human application at 7T has not been fully established, especially within the frontal lobe, where alterations are linked to various neurological and psychiatric disorders.Purpose To explore the feasibility of the interleaved 1H/13C MRS protocol for quantification of cerebral glucose uptake and downstream metabolism at 7T, and to estimate the tricarboxylic acid (TCA) cycle flux (V TCA) for validation.Study Type Prospective.Population Three healthy volunteers (Two females and one male).Field Strength/Sequence 7T; single voxel spectroscopy: ACE-STEAM (indirect 1H-[13C]) and ISIS-DEPT (direct 13C-[1H]).Assessment ACE-STEAM and ISIS-DEPT were applied to acquire the time-resolved spectra in the frontal lobe. 13C-labeled glucose, glutamate, and glutamine fractional enrichment time courses were quantified to estimate V TCA through the one-compartment model.Statistical Tests The relative estimated fitting uncertainties (EFUs) were reported for the processed spectra. Nonlinear least squares minimization was used for flux fitting of 13C traces. Uncertainty of the estimated metabolic fluxes was evaluated using Monte Carlo simulations.Results [1-13C]-glucose (GlcC1) was detected within 6 min on 13C MR spectra, followed by 13C-labeled GluH4 and GlnH4, and then GlxH3 can be quantified on 1H MR spectra. End-of-infusion mean enrichments were 17% (GluH4), 13% (GlnH4), and 7% (GlxH3). Brain glucose concentration ranged 1.86-2.94 mM, with 61% of the mean enrichment in C1. Group-average V TCA was 0.66 +/- 0.07 mu mol/g/min (n = 3).Data Conclusion This interleaved 1H/13C MRS protocol, combined with 13C-labeled glucose infusion, enables minimally invasive quantification of cerebral metabolic fluxes. As a proof-of-concept feasibility study in a small healthy volunteer cohort, it may provide a useful framework for investigating neuropsychiatric and neurodegenerative diseases at 7T.Evidence Level 1.Technical Efficacy Stage 1.
Background ACLR is associated with altered joint loading and increased risk of post-traumatic osteoarthritis. Conventional MRI has limited sensitivity to early meniscal differences because of short-T2 signal decay and magic-angle effects. Purpose To evaluate whether 3D ultrashort echo time imaging-based adiabatic T1rho (UTE-Adiab-T1rho) and ultrashort echo time imaging-based macromolecular fraction (UTE-MMF) identify regional quantitative MRI differences after ACLR. Study Type Prospective longitudinal cohort study. Population 30 control scans, 19 ACLR scans at 6-12 months, and 13 ACLR scans at 12+ months were analyzed. Mean ages were 34.5, 34.5, and 37.2 years; female/male counts were 15/15, 9/10, and 8/5.Field Strength/Sequence Participants underwent 3-T knee MRI with 3D fat-saturated UTE-Adiab-T1rho and UTE magnetization transfer sequences.Assessment UTE-Adiab-T1rho and UTE-MMF maps were generated with single-component exponential and two-pool magnetization transfer models. Values were extracted from four meniscal regions of interest by a blinded reader, with blinded redelineation in a subset. Patient-reported outcomes included International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, and Western Ontario and McMaster Universities Osteoarthritis Index scores. Statistical Tests Linear mixed-effects models accounted for repeated observations. Benjamini-Hochberg FDR correction was applied. Results UTE-Adiab-T1rho showed significant group (q = 0.001) and region (q < 0.001) effects. Compared with controls, UTE-Adiab-T1rho was higher in LAM at 6-12 months (+5.60 ms; q = 0.035) and 12+ months (+7.09 ms; q = 0.028), and in LPM at 12+ months (+6.35 ms; q = 0.035). UTE-MMF showed significant group (q = 0.041) and region (q < 0.001) effects. LPM UTE-MMF was lower than controls at 6-12 months (-3.56 percentage points; q = 0.028) and 12+ months (-3.10 percentage points; q = 0.049). No 6-12 versus 12+ month MRI or PROM contrast survived FDR correction. MRI-PROM associations were not FDR-significant (all q >= 0.383). Data Conclusion UTE-Adiab-T1rho and UTE-MMF mapping identified regional MRI differences after ACLR. Pairwise differences were concentrated in lateral regions, but corrected group-by-region interactions were not significant. PROMs were worse after ACLR but did not differ between postoperative windows after correction. Evidence Level 2. Technical Efficacy Stage 2.
