Josephine H. Naish

BACKGROUND: Extracellular matrix expansion is a key element of ventricular remodeling and a potential therapeutic target. Cardiovascular magnetic resonance (CMR) T1-mapping techniques are increasingly used to evaluate myocardial extracellular volume (ECV); however, the most widely applied methods are without histological validation. Our aim was to perform comprehensive validation of (1) dynamic-equilibrium CMR (DynEq-CMR), where ECV is quantified using hematocrit-adjusted myocardial and blood T1 values measured before and after gadolinium bolus; and (2) isolated measurement of myocardial T1, used as an ECV surrogate. METHODS AND RESULTS: Whole-heart histological validation was performed using 96 tissue samples, analyzed for picrosirius red collagen volume fraction, obtained from each of 16 segments of the explanted hearts of 6 patients undergoing heart transplantation who had prospectively undergone CMR before transplantation (median interval between CMR and transplantation, 29 days). DynEq-CMR-derived ECV was calculated from T1 measurements made using a modified Look-Locker inversion recovery sequence before and 10 and 15 minutes post contrast. In addition, ECV was measured 2 to 20 minutes post contrast in 30 healthy volunteers. There was a strong linear relationship between DynEq-CMR-derived ECV and histological collagen volume fraction (P<0.001; within-subject: r=0.745; P<0.001; r(2)=0.555 and between-subject: r=0.945; P<0.01; r(2)=0.893; for ECV calculated using 15-minute postcontrast T1). Correlation was maintained throughout the entire heart. Isolated postcontrast T1 measurement showed significant within-subject correlation with histological collagen volume fraction (r=-0.741; P<0.001; r(2)=0.550 for 15-minute postcontrast T1), but between-subject correlations were not significant. DynEq-CMR-derived ECV varied significantly according to contrast dose, myocardial region, and sex. CONCLUSIONS: DynEq-CMR-derived ECV shows a good correlation with histological collagen volume fraction throughout the whole heart. Isolated postcontrast T1 measurement is insufficient for ECV assessment.

Background Blood–brain barrier (BBB) disruption has been noted in animal models of Parkinson’s disease (PD) and forms the basis of the vascular hypothesis of neurodegeneration, yet clinical studies are lacking. Objective To determine alterations in BBB integrity in PD, with comparison to cerebrovascular disease. Methods Dynamic contrast enhanced magnetic resonance images were collected from 49 PD patients, 15 control subjects with cerebrovascular disease [control positive (CP)] and 31 healthy control subjects [control negative (CN)], with all groups matched for age. Quantitative maps of the contrast agent transfer coefficient across the BBB ( K trans ) and plasma volume (v p ) were produced using Patlak analysis. Differences in K trans and v p were assessed with voxel-based analysis as well as in regions associated with PD pathophysiology. In addition, the volume of white matter lesions (WMLs) was obtained from T 2 -weighted fluid attenuation inversion recovery (FLAIR) images. Results Higher K trans , reflecting higher BBB leakage, was found in the PD group than in the CN group using voxel-based analysis; differences were most prominent in the posterior white matter regions. Region of interest analysis confirmed K trans to be significantly higher in PD than in CN, predominantly driven by differences in the substantia nigra, normal-appearing white matter, WML and the posterior cortex. WML volume was significantly higher in PD compared to CN. K trans values and WML volume were similar in PD and CP, suggesting a similar burden of cerebrovascular disease despite lower cardiovascular risk factors. Conclusion These results show BBB disruption in PD.