DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia (DECONNECT): research protocol for a cross-sectional pilot study.

INTRODUCTION: Pre-eclampsia is a hypertensive disorder affecting up to 8% of pregnancies. After pre-eclampsia, women are at increased risk of cognitive problems, and cerebrovascular and cardiovascular disorders. These sequelae could result from microvascular dysfunction persisting after pre-eclampsia. This study will explore differences in cerebral and myocardial microvascular function between women after pre-eclampsia and women after normotensive gestation. We hypothesise that pre-eclampsia alters cerebral and myocardial microvascular functions, which in turn are related to diminished cognitive and cardiac performance. METHODS AND ANALYSIS: The cross-sectional 'DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia' (DECONNECT) pilot study includes women after pre-eclampsia and controls after normotensive pregnancy between 6 months and 20 years after gestation. We recruit women from the Queen of Hearts study, a study investigating subclinical heart failure after pre-eclampsia. Neuropsychological tests are employed to assess different cognitive domains, including attention, processing speed, and cognitive control. Cerebral images are recorded using a 7 Tesla MRI to assess blood-brain barrier integrity, perfusion, blood flow, functional and structural networks, and anatomical dimensions. Cardiac images are recorded using a 3 Tesla MRI to assess cardiac perfusion, strain, dimensions, mass, and degree of fibrosis. We assess the effect of a history of pre-eclampsia using multivariable regression analyses. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of Maastricht University Medical Centre (METC azM/UM, NL47252.068.14). Knowledge dissemination will include scientific publications, presentations at conferences and public forums, and social media. TRIAL REGISTRATION NUMBER: NCT02347540.

Attenuated cognitive functioning decades after preeclampsia.

BACKGROUND: Preeclampsia, a hypertensive pregnancy disorder, is a leading cause of maternal and fetal morbidity and mortality, with remote cardio- and cerebrovascular implications. After preeclampsia, women may report serious disabling cognitive complaints, especially involving executive function, but the extent and time course of these complaints are unknown. OBJECTIVE: This study aimed to determine the impact of preeclampsia on perceived maternal cognitive functioning decades after pregnancy. STUDY DESIGN: This study is part of a cross-sectional case-control study named Queen of Hearts (ClinicalTrials.gov Identifier: NCT02347540), a collaboration study of 5 tertiary referral centers within the Netherlands investigating long-term effects of preeclampsia. Eligible participants were female patients aged ≥18 years after preeclampsia and after normotensive pregnancy between 6 months and 30 years after their first (complicated) pregnancy. Preeclampsia was defined as new-onset hypertension after 20 weeks of gestation along with proteinuria, fetal growth restriction, or other maternal organ dysfunction. Women with a history of hypertension, autoimmune disease, or kidney disease before their first pregnancy were excluded. Attenuation of higher-order cognitive functions, that is, executive function, was measured with the Behavior Rating Inventory of Executive Function for Adults. Crude and covariate-adjusted absolute and relative risks of clinical attenuation over time after (complicated) pregnancy were determined with moderated logistic and log-binomial regression. RESULTS: This study included 1036 women with a history of preeclampsia and 527 women with normotensive pregnancies. Regarding overall executive function, 23.2% (95% confidence interval, 19.0-28.1) of women experienced clinically relevant attenuation after preeclampsia, as opposed to 2.2% (95% confidence interval, 0.8-6.0) of controls immediately after childbirth (adjusted relative risk, 9.20 [95% confidence interval, 3.33-25.38]). Group differences diminished yet remained statistically significant (P < .05) at least 19 years postpartum. Regardless of history of preeclampsia, women with lower educational attainment, mood or anxiety disorders, or obesity were especially at risk. Neither severity of preeclampsia, multiple gestation, method of delivery, preterm birth, nor perinatal death was related to overall executive function. CONCLUSION: After preeclampsia, women were 9 times more likely to experience clinical attenuation of higher-order cognitive functions as opposed to after normotensive pregnancy. Despite overall steady improvement, elevated risks persisted over decades after childbirth.

7T dynamic contrast-enhanced MRI for the detection of subtle blood-brain barrier leakage.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage. METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2* degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack. RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue. CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

Time-efficient measurement of subtle blood-brain barrier leakage using a T1 mapping MRI protocol at 7 T.

PURPOSE: Blood-brain barrier (BBB) disruption is commonly measured with DCE-MRI using continuous dynamic scanning. For precise measurement of subtle BBB leakage, a long acquisition time (>20 minutes) is required. As extravasation of the contrast agent is slow, discrete sampling at strategic time points might be beneficial, and gains scan time for additional sequences. Here, we aimed to explore the feasibility of a sparsely sampled MRI protocol at 7 T. METHODS: The scan protocol consisted of a precontrast quantitative T1 measurement, using an MP2RAGE sequence, and after contrast agent injection, a fast-sampling dynamic gradient-echo perfusion scan and two postcontrast quantitative T1 measurements were applied. Simulations were conducted to determine the optimal postcontrast sampling time points for measuring subtle BBB leakage. The graphical Patlak approach was used to quantify the leakage rate (Ki ) and blood plasma volume (vp ) of normal-appearing white and gray matter. RESULTS: The simulations showed that two postcontrast T1 maps are sufficient to detect subtle leakage, and most sensitive when the last T1 map is acquired late, approximately 30 minutes, after contrast agent administration. The in vivo measurements found Ki and vp values in agreement with other studies, and significantly higher values in gray matter compared with white matter (both p = .04). CONCLUSION: The sparsely sampled protocol was demonstrated to be sensitive to quantify subtle BBB leakage, despite using only three T1 maps. Due to the time-efficiency of this method, it will become more feasible to incorporate BBB leakage measurements in clinical research MRI protocols.

Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study.

BACKGROUND AND PURPOSE: In 30% of the patients with focal epilepsy, an epileptogenic lesion cannot be visually detected with structural MRI. Ultra-high field MRI may be able to identify subtle pathology related to the epileptic focus. We set out to assess 7T MRI-derived volumetric and functional activity lateralization of the hippocampus, hippocampal subfields, temporal and frontal lobe in healthy subjects and MRI-negative patients with focal epilepsy. METHODS: Twenty controls and 10 patients with MRI-negative temporal or frontal lobe epilepsy (TLE and FLE, respectively) underwent a 7T MRI exam. T1 -weigthed imaging and resting-state fMRI was performed. T1 -weighted images were segmented to yield volumes, while from fMRI data, the fractional amplitude of low frequency fluctuations was calculated. Subsequently, volumetric and functional lateralization was calculated from left-right asymmetry. RESULTS: In controls, volumetric lateralization was symmetric, with a slight asymmetry of the hippocampus and subiculum, while functional lateralization consistently showed symmetry. Contrarily, in epilepsy patients, regions were less symmetric. In TLE patients with known focus, volumetric lateralization in the hippocampus and hippocampal subfields was indicative of smaller ipsilateral volumes. These patients also showed clear functional lateralization, though not consistently ipsilateral or contralateral to the epileptic focus. TLE patients with unknown focus showed an obvious volumetric lateralization, facilitating the localization of the epileptic focus. Lateralization results in the FLE patients were less consistent with the epileptic focus. CONCLUSION: MRI-derived volume and fluctuation amplitude are highly symmetric in controls, whereas in TLE, volumetric and functional lateralization effects were observed. This highlights the potential of the technique.

Concurrent Respiratory Motion Correction of Abdominal PET and Dynamic Contrast-Enhanced-MRI Using a Compressed Sensing Approach.

We present an approach for concurrent reconstruction of respiratory motion-compensated abdominal dynamic contrast-enhanced (DCE)-MRI and PET data in an integrated PET/MR scanner. The MR and PET reconstructions share the same motion vector fields derived from radial MR data; the approach is robust to changes in respiratory pattern and does not increase the total acquisition time. Methods: PET and DCE-MRI data of 12 oncologic patients were simultaneously acquired for 6 min on an integrated PET/MR system after administration of 18F-FDG and gadoterate meglumine. Golden-angle radial MR data were continuously acquired simultaneously with PET data and sorted into multiple motion phases on the basis of a respiratory signal derived directly from the radial MR data. The resulting multidimensional dataset was reconstructed using a compressed sensing approach that exploits sparsity among respiratory phases. Motion vector fields obtained using the full 6-min (MC6-min) and only the last 1 min (MC1-min) of data were incorporated into the PET reconstruction to obtain motion-corrected PET images and in an MR iterative reconstruction algorithm to produce a series of motion-corrected DCE-MR images (moco_GRASP). The motion-correction methods (MC6-min and MC1-min) were evaluated by qualitative analysis of the MR images and quantitative analysis of SUVmax and SUVmean, contrast, signal-to-noise ratio (SNR), and lesion volume in the PET images. Results: Motion-corrected MC6-min PET images demonstrated 30%, 23%, 34%, and 18% increases in average SUVmax, SUVmean, contrast, and SNR and an average 40% reduction in lesion volume with respect to the non-motion-corrected PET images. The changes in these figures of merit were smaller but still substantial for the MC1-min protocol: 19%, 10%, 15%, and 9% increases in average SUVmax, SUVmean, contrast, and SNR; and a 28% reduction in lesion volume. Moco_GRASP images were deemed of acceptable or better diagnostic image quality with respect to conventional breath-hold Cartesian volumetric interpolated breath-hold examination acquisitions. Conclusion: We presented a method that allows the simultaneous acquisition of respiratory motion-corrected diagnostic quality DCE-MRI and quantitatively accurate PET data in an integrated PET/MR scanner with negligible prolongation in acquisition time compared with routine PET/DCE-MRI protocols.