Velocity Pulsatility and Arterial Distensibility Along the Internal Carotid Artery

Background Attenuation of velocity pulsatility along the internal carotid artery (ICA) is deemed necessary to protect the microvasculature of the brain. The role of the carotid siphon within the whole ICA trajectory in pulsatility attenuation is still poorly understood. This study aims to assess arterial variances in velocity pulsatility and distensibility over the whole ICA trajectory, including effects of age and sex. Methods and Results We assessed arterial velocity pulsatility and distensibility using flow-sensitized 2-dimensional phase-contrast 3.0 Tesla magnetic resonance imaging in 118 healthy participants. Velocity pulsatility index (vPI=(Vmax-Vmin)/Vmean) and arterial distensibility defined as area pulsatility index (Amax-Amin)/Amean) were calculated at C1, C3, and C7 segments of the ICA. vPI increased between C1 and C3 (0.85±0.13 versus 0.93±0.13, P<0.001 for averaged right+left ICA) and decreased between C3 and C7 (0.93±0.13 versus 0.84±0.13, P<0.001) with overall no effect (C1-C7). Conversely, the area pulsatility index decreased between C1 and C3 (0.18±0.06 versus 0.14±0.04, P<0.001) and increased between C3 and C7 (0.14±0.04 versus 0.31±0.09, P<0.001). vPI in men is higher than in women and increases with age (P<0.015). vPI over the carotid siphon declined with age but remained stable over the whole ICA trajectory. Conclusions Along the whole ICA trajectory, vPI increased from extracranial C1 up to the carotid siphon C3 with overall no effect on vPI between extracranial C1 and intracranial C7 segments. This suggests that the bony carotid canal locally limits the arterial distensibility of the ICA, increasing the vPI at C3 which is consequently decreased again over the carotid siphon. In addition, vPI in men is higher and increases with age

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

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 (N detected), mean blood flow velocity (V mean), 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 V mean (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

Anatomical Markers Associated With the Presence of Intracranial Aneurysms in Individuals Screened for Aneurysms

BACKGROUND Hemodynamic stress is linked to the development of intracranial aneurysms (IAs) and may be influenced by anatomic variation of intracranial arteries. We assessed diameters and bifurcation angles of intracranial arteries forming the circle of Willis in a cohort of individuals screened for the presence of IAs. METHODS Individuals with and without IAs identified at screening with magnetic resonance angiography were compared. Diameters and bifurcation angles of the following arteries were measured using semiautomatic methods: A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery, P1 segments of the posterior cerebral artery, posterior communicating artery (Pcom), internal carotid artery, vertebral artery, and basilar artery. We employed univariate general linear models to assess group differences. This included subgroup comparisons between individuals with IAs at specific locations and matched controls, and comparisons on group level between individuals with and without IAs, corrected for age and sex. RESULTS In 94 of the 1049 individuals (9.0%) included, IAs were detected. Individuals with middle cerebral artery IAs had wider ipsilateral M2–M2 bifurcation angles compared with controls (121±25° versus 97±19°; P<0.01). Individuals with anterior communicating artery IAs showed smaller angles for the A1–A2 bifurcation (106±16° versus 120±17°; P = 0.02), while those with Pcom IAs had wider Pcom–C7 bifurcation angles (147±14° versus 127±17°; P = 0.02) and smaller diameters below the ipsilateral internal carotid artery top (2.86±0.36 mm versus 3.10±0.33 mm; P = 0.03) compared with controls. CONCLUSION We found associations between wider M2–M2 bifurcation angles or narrower A1–A2 bifurcation angles and IA presence, consistent with prior literature. Moreover, we uncovered previously unexplored associations, including wider Pcom–C7 bifurcation angles and smaller internal carotid artery diameters in individuals with Pcom IAs. Future research should explore the potential of these markers in predicting IAs in at‐risk populations during follow‐up screenings

Screening for intracranial aneurysms in persons ⩾35 years with hypertension and atherosclerotic disease who smoke(d)

Introduction: Lifetime risk of aneurysmal subarachnoid haemorrhage (aSAH) is high (7%) in persons ⩾35 years with hypertension who smoke(d). Whether screening for intracranial aneurysms (IAs) to prevent aSAH is effective in these patients is unknown. Patients and methods: Participants were retrieved from a cohort of patients with clinically manifest atherosclerotic vascular disease included between 2012 and 2019 at the University Medical Centre Utrecht (SMART-ORACLE, NCT01932671) in whom CT-angiography (CTA) of intracranial arteries was performed. We selected patients ⩾35 years with hypertension who smoke(d). CTAs were reviewed for the presence of IAs by experienced neuroradiologists. Patients with IAs were offered follow-up imaging to detect aneurysmal growth. We determined aneurysm prevalence and developed a diagnostic model for IA risk at screening using multivariable logistic regression. Results: IA were found in 25 of 500 patients (5.0% prevalence, 95%CI: 3.3%–7.3%). Median 5 year risk of rupture assessed with the PHASES score was 0.9% (IQR: 0.7%–1.3%). During a median follow-up of 57 months (IQR: 39–83 months) no patients suffered from aSAH. Aneurysmal growth was detected in one patient for whom preventive treatment was advised. IA risk at screening ranged between 1.6% and 13.4% with predictors being age, female sex and current smoking. Discussion and conclusion: IA prevalence in persons ⩾35 years with hypertension and atherosclerotic vascular disease who smoke(d) was 5%. Given the very small proportion of IA that needed preventive treatment, we currently do not advise screening for Caucasian persons older than 35 years of age who smoke and have hypertension in general. Whether screening may be effective for certain subgroups (e.g. women older than 50 years of age) or other ethnic populations should be the subject of future studies

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

Assessment of aortic and cerebral haemodynamics and vascular brain injury with 3 and 7 T magnetic resonance imaging in patients with aortic coarctation

Aims: Coarctation of the aorta (CoA) is characterized by a central arteriopathy resulting in increased arterial stiffness. The condition is associated with an increased risk of stroke. We aimed to assess the aortic and cerebral haemodynamics and the presence of vascular brain injury in patients with previous surgical CoA repair. Methods and results: Twenty-seven patients with CoA (median age 22 years, range 12-72) and 25 age-and sex-matched controls (median age 24 years, range 12-64) underwent 3â T (heart, aorta, and brain) and 7â T (brain) magnetic resonance imaging scans. Haemodynamic parameters were measured using two-dimensional phase-contrast images of the ascending and descending aorta, internal carotid artery (ICA), basilar artery (BA), middle cerebral artery (MCA), and perforating arteries. Vascular brain injury was assessed by rating white matter hyperintensities, cortical microinfarcts, lacunes, and microbleeds. Pulse wave velocities in the aortic arch and descending aorta were increased and ascending aortic distensibility was decreased in patients with CoA vs. controls. Patients with CoA showed a higher mean flow velocity in the right ICA, left ICA, and BA and a reduced distensibility in the right ICA, BA, and left MCA. Haemodynamic parameters in the perforating arteries, total cerebral blood flow, intracranial volumes, and vascular brain injury were similar between the groups. Conclusion: Patients with CoA show an increased flow velocity and reduced distensibility in the aorta and proximal cerebral arteries, which suggests the presence of a generalized arteriopathy that extends into the cerebral arterial tree. No substantial vascular brain injury was observed in this relatively young CoA population, although the study was inadequately powered regarding this endpoint

Mapping cerebrovascular hemodynamics with MRI: insights in hemodynamic variation in health and disease

The aim of this thesis was to obtain better insight in the relation between hemodynamics and vascular structure and function in the cerebrovasculature in healthy subjects, in patients with an unruptured intracranial aneurysm (UIA) and in patients with other types of (cerebro)vascular disease. To investigate hemodynamic markers, we used 2D phase-contrast (PC) and 4D PC flow imaging on both 3T and 7T MR field. Hemodynamics and anatomy are directly related to each other in healthy subjects as shown in Chapter 2 and 3, but also in UIA as described in Chapter 5 and 6. However, in cerebrovascular disease (CVD) hemodynamics and anatomy can behave differently, as demonstrated by our findings that show the added value of studying hemodynamics and morphology together. Chapter 7 showed that no effective pulsatility attenuation by the carotid siphon was seen in patients with cerebral small vessel disease (cSVD). Considering the influence of ICA calcification on pulsatility dampening as shown in Chapter 7, the results in Chapter 8 showed that the pulsatility along the ICA siphon is still normally damped in patients with pseudoxanthoma elasticum (PXE). This shows that hemodynamics and morphology in different CVD disease can behave differently along the cerebrovascular tree. Therefore, studying hemodynamics and morphology helps to obtain better understanding of the CVD, and might help in the future for better diagnosis or prognosis of the disease

Aneurysm Prevalence and Quality of Life During Screening in Relatives of Patients With Unruptured Intracranial Aneurysms: A Prospective Study

BACKGROUND AND OBJECTIVES: Screening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives (FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether screening is also effective for FDRs of patients with UIA is unknown. We determined the yield of screening in such FDRs, assessed rupture risk and treatment decisions of aneurysms that were found, identified potential high-risk subgroups, and studied the effects of screening on quality of life (QoL). METHODS: In this prospective cohort study, we included FDRs, aged 20-70 years, of patients with UIA without a family history of aSAH who visited the Neurology outpatient clinic in 1 of 3 participating tertiary referral centers in the Netherlands. FDRs were screened for UIA with magnetic resonance angiography between 2017 and 2021. We determined UIA prevalence and developed a prediction model for UIA risk at screening using multivariable logistic regression. QoL was evaluated with questionnaires 6 times during the first year after screening and assessed with a linear mixed-effects model. RESULTS: We detected 24 UIAs in 23 of 461 screened FDRs, resulting in a 5.0% prevalence (95% CI 3.2-7.4). The median aneurysm size was 3 mm (interquartile range [IQR] 2-4 mm), and the median 5-year rupture risk assessed with the PHASES score was 0.7% (IQR 0.4%-0.9%). All UIAs received follow-up imaging, and none were treated preventively. After a median follow-up of 24 months (IQR 13-38 months), no UIA had changed. Predicted UIA risk at screening ranged between 2.3% and 14.7% with the highest risk in FDRs who smoke and have excessive alcohol consumption (c-statistic: 0.76; 95% CI 0.65-0.88). At all survey moments, health-related QoL and emotional functioning were comparable with those in a reference group from the general population. One FDR with a positive screening result expressed regret about screening. DISCUSSION: Based on the current data, we do not advise screening FDRs of patients with UIA because all identified UIAs had a low rupture risk. We observed no negative effect of screening on QoL. A longer follow-up should determine the risk of aneurysm growth requiring preventive treatment

Anatomical Markers Associated With the Presence of Intracranial Aneurysms in Individuals Screened for Aneurysms

Background Hemodynamic stress is linked to the development of intracranial aneurysms (IAs) and may be influenced by anatomic variation of intracranial arteries. We assessed diameters and bifurcation angles of intracranial arteries forming the circle of Willis in a cohort of individuals screened for the presence of IAs. Methods Individuals with and without IAs identified at screening with magnetic resonance angiography were compared. Diameters and bifurcation angles of the following arteries were measured using semiautomatic methods: A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery, P1 segments of the posterior cerebral artery, posterior communicating artery (Pcom), internal carotid artery, vertebral artery, and basilar artery. We employed univariate general linear models to assess group differences. This included subgroup comparisons between individuals with IAs at specific locations and matched controls, and comparisons on group level between individuals with and without IAs, corrected for age and sex. Results In 94 of the 1049 individuals (9.0%) included, IAs were detected. Individuals with middle cerebral artery IAs had wider ipsilateral M2–M2 bifurcation angles compared with controls (121±25° versus 97±19°; P<0.01). Individuals with anterior communicating artery IAs showed smaller angles for the A1–A2 bifurcation (106±16° versus 120±17°; P = 0.02), while those with Pcom IAs had wider Pcom–C7 bifurcation angles (147±14° versus 127±17°; P = 0.02) and smaller diameters below the ipsilateral internal carotid artery top (2.86±0.36 mm versus 3.10±0.33 mm; P = 0.03) compared with controls. Conclusion We found associations between wider M2–M2 bifurcation angles or narrower A1–A2 bifurcation angles and IA presence, consistent with prior literature. Moreover, we uncovered previously unexplored associations, including wider Pcom–C7 bifurcation angles and smaller internal carotid artery diameters in individuals with Pcom IAs. Future research should explore the potential of these markers in predicting IAs in at‐risk populations during follow‐up screenings