Anita A. Harteveld

Imaging Intracranial Vessel Wall Pathology With Magnetic Resonance Imaging Current Prospects and Future Directions

To date, the probable cause of ischemic stroke is often inferred from the size and location of the infarct, in combination with an evaluation of the heart and the presence of extracranial arterial occlusion or high-grade stenosis.1 Currently used conventional lumenography-based methods such as digital subtraction angiography, computed tomography angiography, and magnetic resonance (MR) angiography are used to determine the presence of such an acute occlusion or high-grade arterial stenosis. From extracranial studies, it is known that luminal narrowing may be absent in patients with severe atherosclerosis owing to arterial remodeling.2–4 Therefore, these methods do not provide information about the underlying pathological processes, which most often involve the vessel wall.5 Vessel wall changes such as vessel wall thickening, enhancement, or the presence of vulnerable atherosclerotic plaques without luminal stenosis are therefore often missed but might be of importance for a better understanding of ischemic stroke.6 Furthermore, intracranial atherosclerosis is an important cause of ischemic stroke7 and often involves the vessel wall. Patients with intracranial atherosclerosis have high recurrent stroke rates,8 and increasingly more attention is being directed to the assessment of the intracranial vessel wall, necessitating an imaging technique directly assessing the intracranial vessel wall. MR imaging (MRI) seems the most promising technique to reliably image intracranial vessel wall pathologies because of its superior soft tissue contrast. Recent advances in MRI9 have made it possible to obtain information about these abnormalities within the intracranial vessel wall, which provides an imaging tool to investigate the role of intracranial vessel wall abnormalities in the diagnosis of stroke. In this review, we discuss the current status of intracranial vessel wall MRI and its potential to identify different intracranial vessel wall pathologies. First, we present the state-of-the-art MRI methods to visualize the intracranial vessel wall …

Neuronal activation induced BOLD and CBF responses upon acetazolamide administration in patients with steno-occlusive artery disease

Blood-oxygenation-level-dependent (BOLD) MRI is widely used for inferring neuronal activation and is becoming increasingly popular for assessing cerebrovascular reactivity (CVR) when combined with a vasoactive stimulus. The BOLD signal contains changes in cerebral blood flow (CBF) and thus information regarding neurovascular coupling and CVR. The BOLD signal, however, is also modulated by changes in cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2), as well as changes in the physiological baseline state. Here, we measured BOLD and CBF responses upon neuronal (visual) activation, before and after a vasodilatory challenge (acetazolamide, ACZ) in patients with vertebrobasilar steno-occlusive disease. After ACZ, the neuronal activation induced BOLD response was reduced or even negative (3 out of 8 subjects), whereas the CBF response remained similar. We show that BOLD alone cannot correctly assess the neuronal activation and underlying neurovascular coupling. The generally assumed positive relationship between BOLD and CBF responses may be severely compromised under changes in the physiological baseline state. Accompanying CBF measurements contain crucial information, and simulations suggest an altered flow-metabolism coupling in these patients.

Patterns of intracranial vessel wall changes in relation to ischemic infarcts.

Objective: In this retrospective case series study, we used 7.0 tesla MRI to describe patterns of intracranial vessel wall abnormalities in relation to ischemic infarcts in 9 patients with different intracranial vessel wall pathologies. Methods: A patient-specific clinical imaging protocol was obtained after regular clinical workup, including a fluid-attenuated inversion recovery and an intracranial vessel wall sequence before and after contrast administration using 7.0 tesla MRI. An attempt was made to describe patterns by grouping the patients by intracranial vessel wall abnormalities (eccentric or concentric; enhancing or nonenhancing), then on the presence of macroinfarcts and cortical microinfarcts (CMIs), and lastly on type of macroinfarct (lacunar, small macroinfarct, or large macroinfarct). Results: Intracranial vessel wall abnormalities were identified in all patients, totaling 45 lesions, 12 of which enhanced after contrast administration. CMIs were found in 5 patients. Two patients had eccentric, enhancing wall thickening but differed based on presence or absence of CMIs. Four patients also had eccentric but nonenhancing wall thickening, 2 of whom showed CMIs. The 2 patients lacking CMIs could be subdivided based on the type of macroinfarct. Concentric, enhanced wall thickening was observed in 2 patients with CMIs who differed regarding macroinfarct types. One patient with previous vasculitis showed concentric, nonenhancing wall thickening. Conclusion: Our results suggest that the combination of intracranial vessel wall abnormalities and infarct type is related to different stroke etiologies.

Quantitative Intracranial Atherosclerotic Plaque Characterization at 7T MRI: An Ex Vivo Study with Histologic Validation

BACKGROUND AND PURPOSE: In recent years, several high-resolution vessel wall MR imaging techniques have emerged for the characterization of intracranial atherosclerotic vessel wall lesions in vivo. However, a thorough validation of MR imaging results of intracranial plaques with histopathology is still lacking. The aim of this study was to characterize atherosclerotic plaque components in a quantitative manner by obtaining the MR signal characteristics (T1, T2, T2*, and proton density) at 7T in ex vivo circle of Willis specimens and using histopathology for validation. MATERIALS AND METHODS: A multiparametric ultra-high-resolution quantitative MR imaging protocol was performed at 7T to identify the MR signal characteristics of different intracranial atherosclerotic plaque components, and using histopathology for validation. In total, 38 advanced plaques were matched between MR imaging and histology, and ROI analysis was performed on the identified tissue components. RESULTS: Mean T1, T2, and T2* relaxation times and proton density values were significantly different between different tissue components. The quantitative T1 map showed the most differences among individual tissue components of intracranial plaques with significant differences in T1 values between lipid accumulation (T1 = 838 ± 167 ms), fibrous tissue (T1 = 583 ± 161 ms), fibrous cap (T1 = 481 ± 98 ms), calcifications (T1 = 314 ± 39 ms), and the intracranial arterial vessel wall (T1 = 436 ± 122 ms). CONCLUSIONS: Different tissue components of advanced intracranial plaques have distinguishable imaging characteristics with ultra-high-resolution quantitative MR imaging at 7T. Based on this study, the most promising method for distinguishing intracranial plaque components is T1-weighted imaging.

High-Resolution Postcontrast Time-of-Flight MR Angiography of Intracranial Perforators at 7.0 Tesla

Background and Purpose Different studies already demonstrated the benefits of 7T for precontrast TOF-MRA in the visualization of intracranial small vessels. The aim of this study was to assess the performance of high-resolution 7T TOF-MRA after the administration of a gadolinium-based contrast agent in visualizing intracranial perforating arteries. Materials and Methods Ten consecutive patients (7 male; mean age, 50.4 ± 9.9 years) who received TOF-MRA at 7T after contrast administration were retrospectively included in this study. Intracranial perforating arteries, branching from the parent arteries of the circle of Willis, were identified on all TOF-MRA images. Provided a TOF-MRA before contrast administration was present, a direct comparison between pre- and postcontrast TOF-MRA was made. Results It was possible to visualize intracranial perforating arteries branching off from the entire circle of Willis, and their proximal branches. The posterior cerebral artery (P1 and proximal segment of P2) appeared to have the largest number of visible perforating branches (mean of 5.1 in each patient, with a range of 2–7). The basilar artery and middle cerebral artery (M1 and proximal segment M2) followed with a mean number of 5.0 and 3.5 visible perforating branches (range of 1–9 and 1–8, respectively). Venous contamination in the postcontrast scans sometimes made it difficult to discern the arterial or venous nature of a vessel. Conclusion High-resolution postcontrast TOF-MRA at 7T was able to visualize multiple intracranial perforators branching off from various parts of the circle of Willis and proximal intracranial arteries. Although confirmation in a larger study is needed, the administration of a contrast agent for high-resolution TOF-MRA at 7T seems to enable a better visualization of the distal segment of certain intracranial perforators.

7-T MRI in Cerebrovascular Diseases: Challenges to Overcome and Initial Results.

Abstract Magnetic resonance imaging (MRI) plays a key role in the investigation of cerebrovascular diseases. Compared with computed tomography (CT) and digital subtraction angiography (DSA), its advantages in diagnosing cerebrovascular pathology include its superior tissue contrast, its ability to visualize blood vessels without the use of a contrast agent, and its use of magnetic fields and radiofrequency pulses instead of ionizing radiation. In recent years, ultrahigh field MRI at 7 tesla (7 T) has shown promise in the diagnosis of many cerebrovascular diseases. The increased signal-to-noise ratio (SNR; 2.3x and 4.7x increase compared with 3 and 1.5 T, respectively) and contrast-to-noise ratio (CNR) at this higher field strength can be exploited to obtain a higher spatial resolution and higher lesion conspicuousness, enabling assessment of smaller brain structures and lesions. Cerebrovascular diseases can be assessed at different tissue levels; for instance, changes of the arteries feeding the brain can be visualized to determine the cause of ischemic stroke, regional changes in brain perfusion can be mapped to predict outcome after revascularization, and tissue damage, including old and recent ischemic infarcts, can be evaluated as a marker of ischemic burden. For the purpose of this review, we will discriminate 3 levels of assessment of cerebrovascular diseases using MRI: Pipes, Perfusion, and Parenchyma (3 Ps). The term Pipes refers to the brain-feeding arteries from the heart and aortic arch, upwards to the carotid arteries, vertebral arteries, circle of Willis, and smaller intracranial arterial branches. Perfusion is the amount of blood arriving at the brain tissue level, and includes the vascular reserve and perfusion territories. Parenchyma refers to the acute and chronic burden of brain tissue damage, which includes larger infarcts, smaller microinfarcts, and small vessel disease manifestations such as white matter lesions, lacunar infarcts, and microbleeds. In this review, we will describe the key developments in the last decade of 7-T MRI of cerebrovascular diseases, subdivided for these 3 levels of assessment.

Relations between location and type of intracranial atherosclerosis and parenchymal damage

The aim of this study was to assess the relation between location and type of intracranial atherosclerosis (ICAS) and cortical microinfarcts (CMIs) and macroinfarcts in 18 patients presenting with ischemic stroke (n = 12) or transient ischemic attack (TIA) (n = 6) using 7 tesla MR imaging. The protocol included: 3D T2-weighted FLAIR and 3D T1-weighted Magnetization-Preparation Inversion Recovery Turbo Spin Echo sequence. ICAS lesions and infarcts were scored by two raters. The relation between ICAS lesions, calculated ratios of ICAS lesion characteristics, location, and infarcts were examined using linear regression analyses. A total number of 75 ICAS lesions (all patients), 101 CMIs (78% of patients), and 31 macroinfarcts (67% of patients) were found. Seventy-six and sixty-five percent of the CMIs and macroinfarcts, respectively, were found in the same vascular territory as the ICAS lesions (p = 0.977, p = 0.167, respectively). A positive correlation existed between the number of macroinfarcts and CMIs (p < 0.05). In patients with macroinfarcts, we found more concentric (p < 0.01) and diffuse (p < 0.05) type of ICAS lesions. A high prevalence of brain tissue lesions, both macroinfarcts and CMIs, were found in patients with ICAS. Macroinfarcts were found to be related to specific ICAS lesion types. The type of ICAS lesion seems to be promising as a marker for ICAS patients at higher risk of future infarcts.

Arterial spin labelling MRI to measure renal perfusion: a systematic review and statement paper

Abstract Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5–10 min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address.

Detecting Intracranial Vessel Wall Lesions With 7T-Magnetic Resonance Imaging: Patients With Posterior Circulation Ischemia Versus Healthy Controls

Background and Purpose— Vessel wall magnetic resonance imaging sequences have been developed to directly visualize the intracranial vessel wall, enabling detection of vessel wall changes, including those that have not yet caused luminal narrowing. In this study, vessel wall lesion burden was assessed in patients with recent posterior circulation ischemia using 7T-magnetic resonance imaging and compared with matched healthy controls. Methods— Fifty subjects (25 patients and 25 matched healthy controls) underwent 7T-magnetic resonance imaging with an intracranial vessel wall sequence before and after contrast administration. Two raters scored the presence and contrast enhancement of arterial wall lesions in individual segments of the circle of Willis and its primary branches. Total burden and distribution of vessel wall lesions and lesion characteristics (configuration, thickening pattern, and contrast enhancement) were compared both between and within both groups. Results— Overall, vessel wall lesion burden and distribution were comparable between patients and controls. Regarding individual arterial segments, only vessel wall lesions in the posterior cerebral artery were more frequently observed in patients (18.0%) than in controls (5.4%; P=0.003). Many of these lesions showed enhancement, both in patients (48.9%) and in controls (43.5%; P=0.41). In patients, the proportion of enhancing lesions was higher in the posterior circulation (53.3%) than in the anterior circulation (20.6%; P=0.008). Conclusions— Although overall intracranial vessel wall lesion burden and contrast enhancement were comparable between patients with recent posterior circulation ischemia and healthy controls, this study also revealed significant differences between the 2 groups, suggesting an association between posterior circulation lesion burden/enhancement and ischemic events. Clinical Trial Registration— URL: http://www.trialregister.nl. Unique identifier: NTR5688.

High resolution 7T and 9.4T-MRI of human cerebral arterial casts enables accurate estimations of the cerebrovascular morphometry

Quantitative data on the morphology of the cerebral arterial tree could aid in modelling and understanding cerebrovascular diseases, but is scarce in the range between 200 micrometres and 1 mm diameter arteries. Traditional manual measurements are difficult and time consuming. 7T-MRI and 9.4T-MRI of human cerebral arterial plastic casts could proof feasible for acquiring detailed morphological data of the cerebral arterial tree in a time efficient method. One cast of the complete human cerebral arterial circulation embedded in gadolinium-containing gelatine gel was scanned at 7T-MRI (0.1 mm isotropic resolution). A small section of another cast was scanned at 9.4T-MRI (30 µm isotropic resolution). Subsequent 3D-reconstruction was performed using a semi-automatic approach. Validation of 7T-MRI was performed by comparing the radius calculated using MRI to manual measurements on the same cast. As manual measurement of the small section was not feasible, 9.4T-MRI was validated by scanning the small section both at 7T-MRI and 9.4T MRI and comparing the diameters of arterial segments. Linear regression slopes were 0.97 (R-squared 0.94) and 1.0 (R-squared 0.90) for 7T-MRI and 9.4T-MRI. This data shows that 7T-MRI and 9.4T-MRI and subsequent 3D reconstruction of plastic casts is feasible, and allows for characterization of human cerebral arterial tree morphology.