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.

Cerebral Microvascular Perfusion Assessed in Elderly Adults by Spin-Echo Dynamic Susceptibility Contrast MRI at 7 Tesla.

Perfusion measures of the total vasculature are commonly derived with gradient-echo (GE) dynamic susceptibility contrast (DSC) MR images, which are acquired during the early passes of a contrast agent. Alternatively, spin-echo (SE) DSC can be used to achieve specific sensitivity to the capillary signal. For an improved contrast-to-noise ratio, ultra-high-field MRI makes this technique more appealing to study cerebral microvascular physiology. Therefore, this study assessed the applicability of SE-DSC MRI at 7 T. Forty-one elderly adults underwent 7 T MRI using a multi-slice SE-EPI DSC sequence. The cerebral blood volume (CBV) and cerebral blood flow (CBF) were determined in the cortical grey matter (CGM) and white matter (WM) and compared to values from the literature. The relation of CBV and CBF with age and sex was investigated. Higher CBV and CBF values were found in CGM compared to WM, whereby the CGM-to-WM ratios depended on the amount of largest vessels excluded from the analysis. CBF was negatively associated with age in the CGM, while no significant association was found with CBV. Both CBV and CBF were higher in women compared to men in both CGM and WM. The current study verifies the possibility of quantifying cerebral microvascular perfusion with SE-DSC MRI at 7 T.

Blood-Brain Barrier Integrity Decreases With Higher Blood Pressure: A 7T DCE-MRI Study.

BACKGROUND: Blood-brain barrier (BBB) integrity is presumed to be impaired in hypertension, resulting from cerebral endothelial dysfunction. Hypertension precedes various cerebrovascular diseases, such as cerebral small vessel disease, and is a risk factor for developing neurodegenerative diseases for which BBB disruption is a preceding pathophysiological process. In this cross-sectional study, we investigated the relation between hypertension, current blood pressure, and BBB leakage in human subjects. METHODS: BBB leakage was determined in 22 patients with hypertension and 19 age- and sex-matched normotensive controls (median age [range], 65 [45-80] years; 19 men) using a sparsely time-sampled contrast-enhanced 7T magnetic resonance imaging protocol. Structural cerebral small vessel disease markers were visually rated. Multivariable regression analyses, adjusted for age, sex, cardiovascular risk factors, and cerebral small vessel disease markers, were performed to determine the relation between hypertension status, systolic and diastolic blood pressure, mean arterial pressure, drug treatment, and BBB leakage. RESULTS: Both hypertensive and normotensive participants showed mild scores of cerebral small vessel disease. BBB leakage did not differ between hypertensive and normotensive participants; however, it was significantly higher for systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the cortex, and diastolic blood pressure and mean arterial pressure in the gray matter. Effectively treated patients showed less BBB leakage than those with current hypertension. CONCLUSIONS: BBB integrity in the total and cortical gray matter decreases with increasing blood pressure but is not related to hypertension status. These findings show that BBB disruption already occurs with increasing blood pressure, before the presence of overt cerebral tissue damage. Additionally, our results suggest that effective antihypertensive medication has a protective effect on the BBB. REGISTRATION: URL: https://trialsearch.who.int/; Unique identifier: NL7537.

1D versus 3D blood flow velocity and pulsatility measurements of lenticulostriate arteries at 7T MRI.

PURPOSE: 7T MRI enables measurements of blood flow velocity waveforms in small, perforating cerebral arteries. As these vessels can be tortuous, acquisition methods sensitive to flow in only one direction may not be sufficient to accurately determine the dynamic blood flow velocity. In this study, we compared 1D with 3D velocity encoding to measure the blood flow velocity and pulsatility in the lenticulostriate arteries (LSAs). METHODS: Blood flow velocity waveforms were measured in the LSAs of 18 subjects (age range: 20-74 years) using prospectively gated single-slice phase contrast (PC) MRI at 7T. For each subject, blood flow velocity waveforms were acquired in a single slice with one velocity encoding as well as three orthogonal velocity encodings. The peak velocity and pulsatility index (PI) were determined in the largest, perpendicularly planned LSA, one obliquely planned LSA and three smaller LSAs. The peak velocity and PI were compared between 1D and 3D measurements using Bland-Altman analysis, with the 95% limits of agreement (LOA) taken into account. RESULTS: For the largest, perpendicularly planned LSA, the peak velocity was slightly lower (0.2 cm/s, 1.7%) for 1D compared to 3D measurements, with an LOA range from the mean difference of (-0.27;0.27). The PI was slightly higher (0.01, 1.6%) for the 1D measurement, and an LOA range from the mean difference in PI of (-0.045;0.045). The obliquely planned LSA and three smaller LSAs demonstrated larger deviations (range mean percentage difference: 3.9-8.2%). CONCLUSION: 1D velocity encoding using 2D PC MRI provides sufficiently accurate dynamic velocity and pulsatility measurements in slices perpendicularly planned to single, large LSAs compared to 3D velocity encoding, while increasing errors are obtained with obliquely planned slices. A greater error is indicated when measuring multiple (possibly tortuous or obliquely planned) smaller LSAs in one scan using one-directional single-slice PC MRI.

Hypertension Correlates With Stronger Blood Flow Pulsatility in Small Perforating Cerebral Arteries Assessed With 7 Tesla Magnetic Resonance Imaging.

BACKGROUND: Hypertension alters the structure and function of cerebral blood vessels, and is an important risk factor for stroke and cerebral small vessel disease (cSVD). However, the pathophysiological process is not yet well understood. This study aimed to investigate the relationship between the pulsatility measures in small perforating arteries and hypertension, since hypertension-induced arterial stiffening may lead to a higher blood flow pulsatility and lower damping. METHODS: We examined 28 patients with essential hypertension and 25 age- and sex-matched healthy controls (mean age: 63.4, range: 43-81 years, 26 males). Blood flow velocity waveforms were acquired in the lenticulostriate arteries (LSAs) and the middle cerebral artery using phase-contrast MRI at 7 Tesla. Several cSVD markers were scored. The velocity and pulsatility measures were compared between the hypertensives and controls. RESULTS: A higher pulsatility index (PI) in the LSAs and a lower damping factor (DF) was found in the hypertensive compared to the normotensive group (P=0.015, P=0.015, respectively), but no association was found for the PI in the middle cerebral artery. Higher systolic and mean arterial pressures were associated with higher PI in the LSA and DF. For diastolic blood pressure, only an association with a lower DF was found. Adjusting for cSVD score did not alter these relationships. CONCLUSIONS: This study shows a higher PI in the LSAs and a lower DF in subjects with hypertension, independent of cSVD presence. This supports the hypothesis that hypertension-induced arterial remodeling may alter the intracerebral blood flow velocity profiles, which could eventually contribute to cerebral tissue damage. REGISTRATION: URL: https://trialsearch.who.int/; Unique identifier: NL7537 and NL8798.

Impaired damping of cerebral blood flow velocity pulsatility is associated with the number of perivascular spaces as measured with 7T MRI.

Arterial walls stiffen with age, cardiovascular risk factors, and various vascular diseases, which may lead to less damping of the arterial blood flow pulse, subsequent microvascular damage, and enlarged perivascular spaces (PVS). However, the exact interplay between these processes is unclear. This study aimed to investigate the relation between blood flow velocity pulsatility in the small lenticulostriate arteries and their supplying middle cerebral artery and the respective damping factor (DF), with the number of MRI-visible PVS in elderly subjects. Blood flow velocity waveforms were obtained in 45 subjects (median age [range]: 64 [48-81] years, 47% male) using 7T MRI. PVS were scored in the basal ganglia (BG) and centrum semiovale (CSO). Spearman correlation analyses were used to determine associations of the blood flow pulsatility and the DF, with PVS score, adjusted for age and sex. We found a significant association between a lower DF and a higher number of PVS in the BG (rs = -0.352, P = 0.021), but not in the CSO. This finding supports the supposed pathophysiological mechanism in which excessive kinetic energy deposition leads to damage of small perforating arteries and contributes to the enlargement of PVS at the level of the BG, but possible other pathways might also be of influence.

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.