CADASIL Affects Multiple Aspects of Cerebral Small Vessel Function on 7T-MRI.

OBJECTIVE: Cerebral small vessel diseases (cSVDs) are a major cause of stroke and dementia. We used cutting-edge 7T-MRI techniques in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), to establish which aspects of cerebral small vessel function are affected by this monogenic form of cSVD. METHODS: We recruited 23 CADASIL patients (age 51.1 ± 10.1 years, 52% women) and 13 age- and sex-matched controls (46.1 ± 12.6, 46% women). Small vessel function measures included: basal ganglia and centrum semiovale perforating artery blood flow velocity and pulsatility, vascular reactivity to a visual stimulus in the occipital cortex and reactivity to hypercapnia in the cortex, subcortical gray matter, white matter, and white matter hyperintensities. RESULTS: Compared with controls, CADASIL patients showed lower blood flow velocity and higher pulsatility index within perforating arteries of the centrum semiovale (mean difference - 0.09 cm/s, p = 0.03 and 0.20, p = 0.009) and basal ganglia (mean difference - 0.98 cm/s, p = 0.003 and 0.17, p = 0.06). Small vessel reactivity to a short visual stimulus was decreased (blood-oxygen-level dependent [BOLD] mean difference -0.21%, p = 0.04) in patients, while reactivity to hypercapnia was preserved in the cortex, subcortical gray matter, and normal appearing white matter. Among patients, reactivity to hypercapnia was decreased in white matter hyperintensities compared to normal appearing white matter (BOLD mean difference -0.29%, p = 0.02). INTERPRETATION: Multiple aspects of cerebral small vessel function on 7T-MRI were abnormal in CADASIL patients, indicative of increased arteriolar stiffness and regional abnormalities in reactivity, locally also in relation to white matter injury. These observations provide novel markers of cSVD for mechanistic and intervention studies. ANN NEUROL 2023;93:29-39.

CO2 as an engine for neurofluid flow: Exploring the coupling between vascular reactivity, brain clearance, and changes in tissue properties.

The brain relies on an effective clearance mechanism to remove metabolic waste products for the maintenance of homeostasis. Recent studies have focused on elucidating the forces that drive the motion of cerebrospinal fluid (CSF), responsible for removal of these waste products. We demonstrate that vascular responses evoked using controlled manipulations of partial pressure of carbon dioxide (PaCO2) levels, serve as an endogenous driver of CSF clearance from the brain. To demonstrate this, we retrospectively surveyed our database, which consists of brain metastases patients from whom blood oxygen level-dependent (BOLD) images were acquired during targeted hypercapnic and hyperoxic respiratory challenges. We observed a correlation between CSF inflow signal around the fourth ventricle and CO2-induced changes in cerebral blood volume. By contrast, no inflow signal was observed in response to the nonvasoactive hyperoxic stimulus, validating our measurements. Moreover, our results establish a link between the rate of the hemodynamic response (to elevated PaCO2) and peritumoral edema load, which we suspect may affect CSF flow, consequently having implications for brain clearance. Our expanded perspective on the factors involved in neurofluid flow underscores the importance of considering both cerebrovascular responses, as well as the brain mechanical properties, when evaluating CSF dynamics in the context of disease processes.

Hemodynamic Parameters in the Parent Arteries of Unruptured Intracranial Aneurysms Depend on Aneurysm Size and Are Different Compared to Contralateral Arteries: A 7 Tesla 4D Flow MRI Study.

BACKGROUND: Different Circle of Willis (CoW) variants have variable prevalences of aneurysm development, but the hemodynamic variation along the CoW and its relation to presence and size of unruptured intracranial aneurysms (UIAs) are not well known. PURPOSE: Gain insight into hemodynamic imaging markers of the CoW for UIA development by comparing these outcomes to the corresponding contralateral artery without an UIA using 4D flow magnetic resonance imaging (MRI). STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Thirty-eight patients with an UIA, whereby 27 were women and a mean age of 62 years old. FIELD STRENGTH/SEQUENCE: Four-dimensional phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T. ASSESSMENT: Hemodynamic parameters (blood flow, velocity pulsatility index [vPI], mean velocity, distensibility, and wall shear stress [peak systolic (WSSMAX ), and time-averaged (WSSMEAN )]) in the parent artery of the UIA were compared to the corresponding contralateral artery without an UIA and were related to UIA size. STATISTICAL TESTS: Paired t-tests and Pearson Correlation tests. The threshold for statistical significance was P < 0.05 (two-tailed). RESULTS: Blood flow, mean velocity, WSSMAX , and WSSMEAN were significantly higher, while vPI was lower, in the parent artery relative to contralateral artery. The WSSMAX of the parent artery significantly increased linearly while the WSSMEAN decreased linearly with increasing UIA size. CONCLUSIONS: Hemodynamic parameters and WSS differ between parent vessels of UIAs and corresponding contralateral vessels. WSS correlates with UIA size, supporting a potential hemodynamic role in aneurysm pathology. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

The relation between vascular risk factors and flow in cerebral perforating arteries. A 7 Tesla MRI study.

INTRODUCTION: Cerebral perforating arteries provide blood supply to the deep regions of the brain. Recently, it became possible to measure blood flow velocity and pulsatility in these small arteries. It is unknown if vascular risk factors are related to these measures. METHODS: We measured perforating artery flow with 2D phase contrast 7 Tesla MRI at the level of the centrum semiovale (CSO) and the basal ganglia (BG) in seventy participants from the Heart Brain Connection study with carotid occlusive disease (COD), vascular cognitive impairment (VCI), or no actual cerebrovascular disease. Vascular risk factors included hypertension, diabetes, hyperlipidemia and smoking. RESULTS: No consistent relations were found between any of the vascular risk factors and either flow velocity or flow pulsatility, although there was a relation between lower diastolic blood pressure and higher pulse pressure and higher cerebral perforator pulsatility (p=0,045 and p=0,044, respectively) at the BG level. Results were similar in stratified analyses for patients with and without a history of cardiovascular disease, or only COD or VCI. CONCLUSION: We conclude that, cross-sectionally, cerebral perforating artery flow velocity and pulsatility are largely independent of the presence of common vascular risk factors in a population with a mixed vascular burden.

Estimating the viscoelastic properties of the human brain at 7 T MRI using intrinsic MRE and nonlinear inversion.

Intrinsic actuation magnetic resonance elastography (MRE) is a phase-contrast MRI technique that allows for in vivo quantification of mechanical properties of the brain by exploiting brain motion that arise naturally due to the cardiac pulse. The mechanical properties of the brain reflect its tissue microstructure, making it a potentially valuable parameter in studying brain disease. The main purpose of this study was to assess the feasibility of reconstructing the viscoelastic properties of the brain using high-quality 7 T MRI displacement measurements, obtained using displacement encoding with stimulated echoes (DENSE) and intrinsic actuation. The repeatability and sensitivity of the method for detecting normal regional variation in brain tissue properties was assessed as secondary goal. The displacement measurements used in this analysis were previously acquired for a separate study, where eight healthy subjects (27 ± 7 years) were imaged with repeated scans (spatial resolution approx. 2 mm isotropic, temporal resolution 75 ms, motion sensitivity 0.35 mm/2π for displacements in anterior-posterior and left-right directions, and 0.7 mm/2π for feet-head displacements). The viscoelastic properties of the brain were estimated using a subzone based non-linear inversion scheme. The results show comparable consistency to that of extrinsic MRE between the viscoelastic property maps obtained from repeated displacement measurements. The shear stiffness maps showed fairly consistent spatial patterns. The whole-brain repeatability coefficient (RC) for shear stiffness was (mean ± standard deviation) 8 ± 8% relative to the mean whole-brain stiffness, and the damping ratio RC was 28 ± 17% relative to the whole-brain damping ratio. The shear stiffness maps showed similar statistically significant regional trends as demonstrated in a publicly available atlas of viscoelastic properties obtained with extrinsic actuation MRE at 50 Hz. The damping ratio maps showed less consistency, likely due to data-model mismatch of describing the brain as a viscoelastic material under low frequencies. While artifacts induced by fluid flow within the brain remain a limitation of the technique in its current state, intrinsic actuation based MRE allow for consistent and repeatable estimation of the mechanical properties of the brain. The method provides enough sensitivity to investigate regional variation in such properties in the normal brain, which is likely sufficient to also investigate pathological changes.

Reliability of velocity pulsatility in small vessels on 3Tesla MRI in the basal ganglia: a test-retest study.

OBJECTIVE: Recent work showed the feasibility of measuring velocity pulsatility in the perforating arteries at the level of the BG using 3T MRI. However, test-retest measurements have not been performed, yet. This study assessed the test-retest reliability of 3T MRI blood flow velocity measurements in perforating arteries in the BG. MATERIALS AND METHODS: Two-dimensional phase-contrast cardiac gated (2D-PC) images were acquired for 35 healthy controls and repeated with and without repositioning. 2D-PC images were processed and analyzed, to assess the number of detected perforating arteries (Ndetected), mean blood flow velocity (Vmean), and velocity pulsatility index (vPI). Paired t-tests and Bland-Altman plots were used to compare variance in outcome parameters with and without repositioning, and limits of agreement (LoA) were calculated. RESULTS: The LoA was smallest for Vmean (35%) and highest for vPI (79%). Test-retest reliability was similar with and without repositioning of the subject. DISCUSSION: We found similar LoA with and without repositioning indicating that the measurement uncertainty is dominated by scanner and physiological noise, rather than by planning. This enables to study hemodynamic parameters in perforating arteries at clinically available scanners, provided sufficiently large sample sizes are used to mitigate the contribution of scanner- and physiological noise.

Dynamic brain ADC variations over the cardiac cycle and their relation to tissue strain assessed with DENSE at high-field MRI.

PURPOSE: The ADC of brain tissue slightly varies over the cardiac cycle. This variation could reflect physiology, including mixing of the interstitial fluid, relevant for brain waste clearance. However, it is known from cardiac diffusion imaging that tissue deformation by itself affects the magnitude of the MRI signal, leading to artificial ADC variations as well. This study investigates to what extent tissue deformation causes artificial ADC variations in the brain. THEORY AND METHODS: We implemented a high-field MRI sequence with stimulated echo acquisition mode that simultaneously measures brain tissue deformation and ADC. Based on the measured tissue deformation, we simulated the artificial ADC variation by combining established theoretical frameworks and compared the results with the measured ADC variation. We acquired data in 8 healthy volunteers with diffusion weighting b = 300 and b = 1000 s/mm2 . RESULTS: Apparent diffusion coefficient variation was largest in the feet-to-head direction and showed the largest deviation from the mean ADC at peak systole. Artificial ADC variation estimated from tissue deformation was 1.3 ± 0.37·10-5  mm2 /s in the feet-to-head direction for gray matter, and 0.75 ± 0.29·10-5  mm2 /s for white matter. The measured ADC variation in the feet-to-head direction was 5.6·10-5 ± 1.5·10-5  mm2 /s for gray matter and 3.2·10-5 ± 1.0·10-5  mm2 /s for white matter, which was a factor of 3.5 ± 0.82 and 3.4 ± 0.57 larger than the artificial diffusion variations. The measured diffusion variations in the right-to-left/anterior-to-posterior direction were a factor of 1.5 ± 1.0/1.7 ± 1.4 and 2.0 ± 0.91/2.5 ± 0.94 larger than the artificial diffusion variations for gray matter and white matter, respectively. CONCLUSION: Apparent diffusion coefficient variations in the brain likely largely reflect physiology.

Does the Internal Carotid Artery Attenuate Blood-Flow Pulsatility in Small Vessel Disease? A 7 T 4D-Flow MRI Study.

BACKGROUND: Increased cerebral blood-flow pulsatility is associated with cerebral small vessel disease (cSVD). Reduced pulsatility attenuation over the internal carotid artery (ICA) could be a contributing factor to the development of cSVD and could be associated with intracranial ICA calcification (iICAC). PURPOSE: To compare pulsatility, pulsatility attenuation, and distensibility along the ICA between patients with cSVD and controls and to assess the association between iICAC and pulsatility and distensibility. STUDY TYPE: Retrospective, explorative cross-sectional study. SUBJECTS: A total of 17 patients with cSVD, manifested as lacunar infarcts or deep intracerebral hemorrhage, and 17 age- and sex-matched controls. FIELD STRENGTH/SEQUENCE: Three-dimensional (3D) T1-weighted gradient echo imaging and 4D phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T. ASSESSMENT: Blood-flow velocity pulsatility index (vPI) and arterial distensibility were calculated for seven ICA segments (C1-C7). iICAC presence and volume were determined from available brain CT scans (acquired as part of standard clinical care) in patients with cSVD. STATISTICAL TESTS: Independent t-tests and linear mixed models. The threshold for statistically significance was P < 0.05 (two tailed). RESULTS: The cSVD group showed significantly higher ICA vPI and significantly lower distensibility compared to controls. Controls showed significant attenuation of vPI over the carotid siphon (-4.9% ± 3.6%). In contrast, patients with cSVD showed no attenuation, but a significant increase of vPI (+6.5% ± 3.1%). iICAC presence and volume correlated positively with vPI (r = 0.578) in patients with cSVD and negatively with distensibility (r = -0.386). CONCLUSION: Decreased distensibility and reduced pulsatility attenuation are associated with increased iICAC and may contribute to cSVD. Confirmation in a larger prospective study is required. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Non-Invasive Assessment of Damping of Blood Flow Velocity Pulsatility in Cerebral Arteries With MRI.

BACKGROUND: Damping of heartbeat-induced pressure pulsations occurs in large arteries such as the aorta and extends to the small arteries and microcirculation. Since recently, 7 T MRI enables investigation of damping in the small cerebral arteries. PURPOSE: To investigate flow pulsatility damping between the first segment of the middle cerebral artery (M1) and the small perforating arteries using magnetic resonance imaging. STUDY TYPE: Retrospective. SUBJECTS: Thirty-eight participants (45% female) aged above 50 without history of heart failure, carotid occlusive disease, or cognitive impairment. FIELD STRENGTH/SEQUENCE: 3 T gradient echo (GE) T1-weighted images, spin-echo fluid-attenuated inversion recovery images, GE two-dimensional (2D) phase-contrast, and GE cine steady-state free precession images were acquired. At 7 T, T1-weighted images, GE quantitative-flow, and GE 2D phase-contrast images were acquired. ASSESSMENT: Velocity pulsatilities of the M1 and perforating arteries in the basal ganglia (BG) and semi-oval center (CSO) were measured. We used the damping index between the M1 and perforating arteries as a damping indicator (velocity pulsatilityM1 /velocity pulsatilityCSO/BG ). Left ventricular stroke volume (LVSV), mean arterial pressure (MAP), pulse pressure (PP), and aortic pulse wave velocity (PWV) were correlated with velocity pulsatility in the M1 and in perforating arteries, and with the damping index of the CSO and BG. STATISTICAL TESTS: Correlations of LVSV, MAP, PP, and PWV with velocity pulsatility in the M1 and small perforating arteries, and correlations with the damping indices were evaluated with linear regression analyses. RESULTS: PP and PWV were significantly positively correlated to M1 velocity pulsatility. PWV was significantly negatively correlated to CSO velocity pulsatility, and PP was unrelated to CSO velocity pulsatility (P = 0.28). PP and PWV were uncorrelated to BG velocity pulsatility (P = 0.25; P = 0.68). PWV and PP were significantly positively correlated with the CSO damping index. DATA CONCLUSION: Our study demonstrated a dynamic damping of velocity pulsatility between the M1 and small cerebral perforating arteries in relation to proximal stress. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Strain Tensor Imaging: Cardiac-induced brain tissue deformation in humans quantified with high-field MRI.

The cardiac cycle induces blood volume pulsations in the cerebral microvasculature that cause subtle deformation of the surrounding tissue. These tissue deformations are highly relevant as a potential source of information on the brain's microvasculature as well as of tissue condition. Besides, cyclic brain tissue deformations may be a driving force in clearance of brain waste products. We have developed a high-field magnetic resonance imaging (MRI) technique to capture these tissue deformations with full brain coverage and sufficient signal-to-noise to derive the cardiac-induced strain tensor on a voxel by voxel basis, that could not be assessed non-invasively before. We acquired the strain tensor with 3 mm isotropic resolution in 9 subjects with repeated measurements for 8 subjects. The strain tensor yielded both positive and negative eigenvalues (principle strains), reflecting the Poison effect in tissue. The principle strain associated with expansion followed the known funnel shaped brain motion pattern pointing towards the foramen magnum. Furthermore, we evaluate two scalar quantities from the strain tensor: the volumetric strain and octahedral shear strain. These quantities showed consistent patterns between subjects, and yielded repeatable results: the peak systolic volumetric strain (relative to end-diastolic strain) was 4.19⋅10-4 ± 0.78⋅10-4 and 3.98⋅10-4 ± 0.44⋅10-4 (mean ± standard deviation for first and second measurement, respectively), and the peak octahedral shear strain was 2.16⋅10-3 ± 0.31⋅10-3 and 2.31⋅10-3 ± 0.38⋅10-3, for the first and second measurement, respectively. The volumetric strain was typically highest in the cortex and lowest in the periventricular white matter, while anisotropy was highest in the subcortical white matter and basal ganglia. This technique thus reveals new, regional information on the brain's cardiac-induced deformation characteristics, and has the potential to advance our understanding of the role of microvascular pulsations in health and disease.

Double delay alternating with nutation for tailored excitation facilitates banding-free isotropic high-resolution intracranial vessel wall imaging.

The purpose of this study was to evaluate the use of a double delay alternating with nutation for tailored excitation (D-DANTE)-prepared sequence for banding-free isotropic high-resolution intracranial vessel wall imaging (IC-VWI) and to compare its performance with regular DANTE in terms of signal-to-noise ratio (SNR) as well as cerebrospinal fluid (CSF) and blood suppression efficiency. To this end, a D-DANTE-prepared 3D turbo spin echo sequence was implemented by interleaving two separate DANTE pulse trains with different RF phase-cycling schemes, but keeping all other DANTE parameters unchanged, including the total number of pulses and total preparation time. This achieved a reduction of the banding distance compared with regular DANTE enabling banding-free imaging up to higher resolutions. Bloch simulations assuming static vessel wall and flowing CSF spins were performed to compare DANTE and D-DANTE in terms of SNR and vessel wall/CSF contrast. Similar image quality measures were assessed from measurements on 13 healthy middle-aged volunteers. Both simulation and in vivo results showed that D-DANTE had only slightly lower vessel wall/CSF and vessel wall/blood contrast-to-noise ratio values compared with regular DANTE, which originated from a 10%-15% reduction in vessel wall SNR but not from reduced CSF or blood suppression efficiency. As anticipated, IC-VWI acquisitions showed that D-DANTE can successfully remove banding artifacts compared with regular DANTE with equal scan time or DANTE preparation length. Moreover, application was demonstrated in a patient with an intracranial aneurysm, indicating improved robustness to slow flow artifacts compared with clinically available 3D turbo spin echo scans. In conclusion, D-DANTE provides banding artifact-free IC-VWI up to higher isotropic resolutions compared with regular DANTE. This allows for a more flexible choice of DANTE preparation parameters in high-resolution IC-VWI protocols.

Automated Assessment of Cerebral Arterial Perforator Function on 7T MRI.

BACKGROUND: Blood flow velocity and pulsatility of small cerebral perforating arteries can be measured using 7T quantitative 2D phase contrast (PC) MRI. However, ghosting artifacts arising from subject movement and pulsating large arteries cause false positives when applying a previously published perforator detection method. PURPOSE: To develop a robust, automated method to exclude perforators located in ghosting artifacts. STUDY TYPE: Retrospective. SUBJECTS: Fifteen patients with vascular cognitive impairment or carotid occlusive disease and 10 healthy controls. FIELD STRENGTH/SEQUENCE: 7T/cardiac-gated 2D PC MRI. ASSESSMENT: Perforators were automatically excluded from ghosting regions, which were defined as bands in the phase-encoding direction of large arteries. As reference, perforators were manually excluded by two raters (T.A., J.J.M.Z.), based on perforator location with respect to visible ghosting artifacts. The performance of both censoring methods was assessed for the number of (Nincluded ), mean velocity (Vmean ), and pulsatility index (PI) of the included perforators. STATISTICAL TESTS: For within-method comparisons, inter- and intrarater reliability were assessed for the manual method, and test-retest reliability was assessed for both methods from repeated 2D PC scans (without repositioning). Intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CIs) were determined for Nincluded , Vmean , and PI for all within-method comparisons. The ICC to compare between the two methods was determined with the use of both (test-retest) scans using a multilevel nonlinear mixed model. RESULTS: The automated censoring method showed a moderate to good ICC (95% CI) vs. manual censoring for Nincluded (0.73 [0.58-0.87]) and Vmean (0.90 [0.84-0.96]), and a moderate ICC for PI (0.57 [0.37-0.76]). The test-retest reliability of the manual censoring method was considerably lower than the interrater and intrarater reliability, indicating that scanner noise dominates the uncertainty of the analysis. DATA CONCLUSION: The proposed automated censoring method can reliably exclude small perforators affected by ghosting artifacts. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 1.

Cardiac and respiration-induced brain deformations in humans quantified with high-field MRI.

Microvascular blood volume pulsations due to the cardiac and respiratory cycles induce brain tissue deformation and, as such, are considered to drive the brain's waste clearance system. We have developed a high-field magnetic resonance imaging (MRI) technique to quantify both cardiac and respiration-induced tissue deformations, which could not be assessed noninvasively before. The technique acquires motion encoded snapshot images in which various forms of motion and confounders are entangled. First, we optimized the motion sensitivity for application in the human brain. Next, we isolated the heartbeat and respiration-related deformations, by introducing a linear model that fits the snapshot series to the recorded physiological information. As a result, we obtained maps of the physiological tissue deformation with 3mm isotropic spatial resolution. Heartbeat and respiration-induced volumetric strain were significantly different from zero in the basal ganglia (median (25-75% interquartile range): 0.85·10-3 (0.39·10-3-1.05·10-3), p â€‹= â€‹0.0008 and -0.28·10-3 (-0.41·10-3-0.06·10-3), p â€‹= â€‹0.047, respectively. Smaller volumetric strains were observed in the white matter of the centrum semi ovale (0.28·10-3 (0-0.59·10-3) and -0.06·10-3 (-0.17·10-3-0.20·10-3)), which was only significant for the heartbeat (p â€‹= â€‹0.02 and p â€‹= â€‹0.7, respectively). Furthermore, heartbeat-induced volumetric strain was about three times larger than respiration-induced volumetric strain. This technique opens a window on the driving forces of the human brain clearance system.

Validating faster DENSE measurements of cardiac-induced brain tissue expansion as a potential tool for investigating cerebral microvascular pulsations.

Displacement Encoding with Stimulated Echoes (DENSE) has recently shown potential for measuring cardiac-induced cerebral volumetric strain in the human brain. As such, it may provide a powerful tool for investigating the cerebral small vessels. However, further development and validation are necessary. This study aims, first, to validate a retrospectively-gated implementation of the DENSE method for assessing brain tissue pulsations as a physiological marker, and second, to use the acquired measurements to explore intracranial volume dynamics. We acquired repeated measurements of cerebral volumetric strain in 8 healthy subjects, and internally validated these measurements by comparing them to spinal CSF stroke volumes obtained in the same scan session. Peak volumetric strain was found to be highly repeatable between scan sessions. First/second measured peak volumetric strains were: (6.4 â€‹± â€‹1.7)x10-4/(6.7 â€‹± â€‹1.6)x10-4 for whole brain, (9.5 â€‹± â€‹2.5)x10-4/(9.6 â€‹± â€‹2.4)x10-4 for grey matter, and (4.4 â€‹± â€‹1.7)x10-4/(4.1 â€‹± â€‹0.8)x10-4 for white matter. Grey matter showed significantly higher peak strain (p â€‹< â€‹0.001) and earlier time-to-peak strain (p â€‹< â€‹0.02) than white matter. An approximately linear relationship was found between CSF and brain tissue volume pulsations over the cardiac cycle (mean slope and R2 of 0.88 â€‹± â€‹0.23 and 0.89 â€‹± â€‹0.07, respectively). The close similarity between CSF and brain tissue volume pulsations implies limited contributions from large intracranial vessel pulsations, providing further evidence for venous compression as an additional mechanism for maintaining stable intracranial pressures over the cardiac cycle. Cerebral pulsatility showed consistent inter-subject peak values in healthy subjects, and was strongly correlated to CSF stroke volumes. These results strengthen the potential of brain tissue volumetric strain as a means for investigating the intracranial dynamics of the ageing brain in normal or diseased states.

Higher Pulsatility in Cerebral Perforating Arteries in Patients With Small Vessel Disease Related Stroke, a 7T MRI Study.

Background and Purpose- Cerebral small vessel disease (SVD) is a major cause of stroke and dementia, but underlying disease mechanisms are still largely unknown, partly because of the difficulty in assessing small vessel function in vivo. We developed a method to measure blood flow velocity pulsatility in perforating arteries in the basal ganglia and semioval center. We aimed to determine whether this novel method could detect functional abnormalities at the level of the small vessels in patients with stroke attributable to SVD. Methods- We investigated 10 patients with lacunar infarction (mean age 61 years, 80% men), 11 patients with deep intracerebral hemorrhage (ICH) considered to be caused by SVD (ICH, mean age 58 years, 82% men) and 18 healthy controls that were age- and sex-matched. We performed 2-dimensional phase contrast magnetic resonance imaging at 7 T to measure time-resolved blood flow velocity in cerebral perforating arteries of the semioval center and the basal ganglia. We compared the number of detected arteries, pulsatility index and mean velocity between the patient groups and controls. Results- In the basal ganglia, the number of detected perforators was lower in lacunar infarction (26±9, P=0.01) and deep ICH patients (28±6, P=0.02) than in controls (35±7). The pulsatility index in the basal ganglia was higher in lacunar infarction (1.07±0.13, P=0.03), and deep ICH patients (1.02±0.11, P=0.11), than in controls (0.94±0.10). Observations in the semioval center were similar. Number of detected perforators was lower in lacunar infarction (32±18, P=0.06), and deep ICH patients (28±18, P=0.02), than in controls (45±16). The pulsatility index was higher in lacunar infarction (1.18±0.15, P=0.02), and deep ICH patients (1.17±0.14, P=0.045) than in controls (1.08±0.07). No velocity differences were detected. Conclusions- This exploratory study shows that SVD can be expressed in terms of functional measures, such as pulsatility index, which are derived directly from the small vessels themselves. Future studies may use this technique to further unravel the mechanisms underlying SVD.

Quantifying cardiac-induced brain tissue expansion using DENSE.

Brain tissue undergoes viscoelastic deformation and volumetric strain as it expands over the cardiac cycle due to blood volume changes within the underlying microvasculature. Volumetric strain measurements may therefore provide insights into small vessel function and tissue viscoelastic properties. Displacement encoding via stimulated echoes (DENSE) is an MRI technique that can quantify the submillimetre displacements associated with brain tissue motion. Despite previous studies reporting brain tissue displacements using DENSE and other MRI techniques, a complete picture of brain tissue volumetric strain over the cardiac cycle has not yet been obtained. To address this need we implemented 3D cine-DENSE at 7 T and 3 T to investigate the feasibility of measuring cardiac-induced volumetric strain as a marker for small vessel blood volume changes. Volumetric strain over the entire cardiac cycle was computed for the whole brain and for grey and white matter tissue separately in six healthy human subjects. Signal-to-noise ratio (SNR) measurements were used to determine the voxel-wise volumetric strain noise. Mean peak whole brain volumetric strain at 7 T (mean ± SD) was (4.5 ± 1.0) × 10-4 (corresponding to a volume expansion of 0.48 ± 0.1 mL), which is in agreement with literature values for cerebrospinal fluid that is displaced into the spinal canal to maintain a stable intracranial pressure. The peak volumetric strain ratio of grey to white matter was 4.4 ± 2.8, reflecting blood volume and tissue stiffness differences between these tissue types. The mean peak volumetric strains of grey and white matter tissue were found to be significantly different (p < 0.001). The mean SNR at 7 T and 3 T of the DENSE measurements was 22.0 ± 7.3 and 7.0 ± 2.8 respectively, which currently limits a voxel-wise strain analysis at both field strengths. We demonstrate that tissue specific quantification of volumetric strain is feasible with DENSE. This metric holds potential for studying blood volume pulsations in the ageing brain in healthy and diseased states.

Phase contrast MRI measurements of net cerebrospinal fluid flow through the cerebral aqueduct are confounded by respiration.

BACKGROUND: Net cerebrospinal fluid (CSF) flow through the cerebral aqueduct may serve as a marker of CSF production in the lateral ventricles, and changes that occur with aging and in disease. PURPOSE: To investigate the confounding influence of the respiratory cycle on net CSF flow and stroke volume measurements. STUDY TYPE: Cross-sectional study. SUBJECTS: Twelve young, healthy subjects (seven male, age range 19-39 years, average age 28.3 years). FIELD STRENGTH/SEQUENCE: Phase contrast MRI (PC-MRI) measurements were performed at 7T, with and without respiratory gating on expiration and on inspiration. All measurements were repeated. ASSESSMENT: Net CSF flow and stroke volume in the aqueduct, over the cardiac cycle, was determined. STATISTICAL TESTS: Repeatability was determined using the intraclass correlation coefficient (ICC) and linear regression analysis between the repeated measurements. Repeated measures analysis of variance (ANOVA) was performed to compare the measurements during inspiration/expiration/no gating. Linear regression analysis was performed between the net CSF flow difference (inspiration minus expiration) and stroke volume. RESULTS: Net CSF flow (average ± standard deviation) was 0.64 ± 0.32 mL/min (caudal) during expiration, 0.12 ± 0.49 mL/min (cranial) during inspiration, and 0.31 ± 0.18 mL/min (caudal) without respiratory gating. Respiratory gating did not affect stroke volume measurements (41 ± 18, 42 ± 19, 42 ± 19 µL/cycle for expiration, no respiratory gating and inspiration, respectively). Repeatability was best during inspiration (ICC = 0.88/0.56/-0.31 for gating on inspiration/expiration/no gating). A positive association was found between average stroke volume and net flow difference between inspiration and expiration (R = 0.678/0.605, P = 0.015/0.037 for the first/second repeated measurement). DATA CONCLUSION: Measured net CSF flow is confounded by respiration effects. Therefore, net CSF flow measurements with PC-MRI cannot in isolation be directly linked to CSF production. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:433-444.

Vascular reactivity in small cerebral perforating arteries with 7 T phase contrast MRI - A proof of concept study.

Existing cerebrovascular reactivity (CVR) techniques assess flow reactivity in either the largest cerebral vessels or at the level of the parenchyma. We examined the ability of 2D phase contrast MRI at 7 T to measure CVR in small cerebral perforating arteries. Blood flow velocity in perforators was measured in 10 healthy volunteers (mean age 26 years) using a 7 T MR scanner, using phase contrast acquisitions in the semioval center (CSO), the basal ganglia (BG) and the middle cerebral artery (MCA). Changes in flow velocity in response to a hypercapnic breathing challenge were assessed, and expressed as the percentual increase of flow velocity as a function of the increase in end tidal partial pressure of CO2. The hypercapnic challenge increased (fit ±â€¯standard error) flow velocity by 0.7 ±â€¯0.3%/mmHg in the CSO (P < 0.01). Moreover, the number of detected perforators (mean [range]) increased from 63 [27-88] to 108 [61-178] (P < 0.001). In the BG, the hypercapnic challenge increased flow velocity by 1.6 ±â€¯0.5%/mmHg (P < 0.001), and the number of detected perforators increased from 48 [24-66] to 63 [32-91] (P < 0.01). The flow in the MCA increased by 5.2 ±â€¯1.4%/mmHg (P < 0.01). Small vessel specific reactivity can now be measured in perforators of the CSO and BG, using 2D phase contrast at 7 T.

Clinical vascular imaging in the brain at 7T.

Stroke and related cerebrovascular diseases are a major cause of mortality and disability. Even at standard-field-strengths (1.5T), MRI is by far the most sensitive imaging technique to detect acute brain infarctions and to characterize incidental cerebrovascular lesions, such as white matter hyperintensities, lacunes and microbleeds. Arterial time-of-flight (TOF) MR angiography (MRA) can depict luminal narrowing or occlusion of the major brain feeding arteries, and this without the need for contrast administration. Compared to 1.5T MRA, the use of high-field strength (3T) and even more so ultra-high-field strengths (7T), enables the visualization of the lumen of much smaller intracranial vessels, while adding a contrast agent to TOF MRA at 7T may enable the visualization of even more distal arteries in addition to veins and venules. Moreover, with 3T and 7T, the arterial vessel walls beyond the circle of Willis become visible with high-resolution vessel wall imaging. In addition, with 7T MRI, the brain parenchyma can now be visualized on a submillimeter scale. As a result, high-resolution imaging studies of the brain and its blood supply at 7T have generated new concepts of different cerebrovascular diseases. In the current article, we will discuss emerging clinical applications and future directions of vascular imaging in the brain at 7T MRI.

The Use and Pitfalls of Intracranial Vessel Wall Imaging: How We Do It.

Intracranial vessel wall magnetic resonance (MR) imaging has gained much attention in the past decade and has become part of state-of-the-art MR imaging protocols to assist in diagnosing the cause of ischemic stroke. With intracranial vessel wall imaging, vessel wall characteristics have tentatively been described for atherosclerosis, vasculitis, dissections, Moyamoya disease, and aneurysms. With the increasing demand and subsequently increased use of intracranial vessel wall imaging in clinical practice, radiologists should be aware of the choices in imaging parameters and how they affect image quality, the clinical indications, methods of assessment, and limitations in the interpretation of these images. In this How I do It article, the authors will discuss the technical requirements and considerations for vessel wall image acquisition in general, describe their own vessel wall imaging protocol at 3 T and 7 T, show a step-by-step basic assessment of intracranial vessel wall imaging as performed at their institution-including commonly encountered artifacts and pitfalls-and summarize the commonly reported imaging characteristics of various intracranial vessel wall diseases for direct clinical applicability. Finally, future technical and clinical considerations for full implementation of intracranial vessel wall imaging in clinical practice, including the need for histologic validation and acquisition time reduction, will be discussed.