Jill B. De Vis

Mapping of cerebral perfusion territories using territorial arterial spin labeling: techniques and clinical application

A knowledge of the exact cerebral perfusion territory which is supplied by any artery is of great importance in the understanding and diagnosis of cerebrovascular disease. The development and optimization of territorial arterial spin labeling (T‐ASL) MRI techniques in the past two decades have made it possible to visualize and determine the cerebral perfusion territories in individual patients and, more importantly, to do so without contrast agents or otherwise invasive procedures. This review provides an overview of the development of ASL techniques that aim to visualize the general cerebral perfusion territories or the territory of a specific artery of interest. The first efforts of T‐ASL with pulsed, continuous and pseudo‐continuous techniques are summarized and subsequent clinical studies using T‐ASL are highlighted. In the healthy population, the perfusion territories of the brain‐feeding arteries are highly variable. This high variability requires special consideration in specific patient groups, such as patients with cerebrovascular disease, stroke, steno‐occlusive disease of the large arteries and arteriovenous malformations. In the past, catheter angiography with selective contrast injection was the only available method to visualize the cerebral perfusion territories in vivo. Several T‐ASL methods, sometimes referred to as regional perfusion imaging, are now available that can easily be combined with conventional brain MRI examinations to show the relationship between the cerebral perfusion territories, vascular anatomy and brain infarcts or other pathology. Increased availability of T‐ASL techniques on clinical MRI scanners will allow radiologists and other clinicians to gain further knowledge of the relationship between vasculature and patient diagnosis and prognosis. Treatment decisions, such as surgical revascularization, may, in the near future, be guided by information provided by T‐ASL MRI in close correlation with structural MRI and quantitative perfusion information. Copyright

Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates.

PURPOSE The purpose of this study was to evaluate if non-invasive Arterial Spin Labeling MR imaging can be used to assess changes in brain perfusion with age which reflect neonatal brain development. For this purpose regional perfusion values obtained with ASL MR imaging were evaluated as a function of postmenstrual age. MATERIALS AND METHODS Pulsed ASL imaging was performed in 33 neonates with a postmenstrual age from 30 to 53 weeks. Whole brain cerebral blood flow (wbCBF), CBF in the basal ganglia and thalamus (BGT-CBF), in the occipital cortex (OC-CBF) and the frontal cortex (FC-CBF) were measured. Regional CBF values were expressed quantitatively (in ml/100 g min) and relative as a percentage of the wbCBF. RESULTS Mean wbCBF increased significantly from 7±2 ml/100 g min (mean±sd) at 31±2 weeks postmenstrual age to 12±3 ml/100 g min at term-equivalent age (TEA) and 29±9 ml/100 g min at 52±1 weeks postmenstrual age. Relative regional CBF was highest in the BGT at all time-points. Relative OC-and FC-CBF increased significantly from 31±2 weeks postmentrual age to TEA. A significant difference in relative BGT-CBF and OC-CBF was shown between infants at 31±2 weeks postmenstrual age and infants scanned at 52±1 weeks postmenstrual age. Relative perfusion in the BGT measured at TEA was significant different compared to 52±1 weeks postmenstrual age. CONCLUSION In conclusion, regional differences in CBF and changes with postmenstrual age could be detected with ASL in neonates. This suggests that ASL can be used as a non-invasive tool to investigate brain maturation in neonates.

Calibrated MRI to evaluate cerebral hemodynamics in patients with an internal carotid artery occlusion.

The purpose of this study was to assess whether calibrated magnetic resonance imaging (MRI) can identify regional variances in cerebral hemodynamics caused by vascular disease. For this, arterial spin labeling (ASL)/blood oxygen level-dependent (BOLD) MRI was performed in 11 patients (65±7 years) and 14 controls (66±4 years). Cerebral blood flow (CBF), ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were evaluated. The CBF was 34±5 and 36±11 mL/100 g per minute in the ipsilateral middle cerebral artery (MCA) territory of the patients and the controls. Arterial spin labeling CVR was 44±20 and 53±10% per 10 mm Hg ΔEtCO2 in patients and controls. The BOLD CVR was lower in the patients compared with the controls (1.3±0.8 versus 2.2±0.4% per 10 mm Hg ΔEtCO2, P < 0.01). The OEF was 41±8% and 38±6%, and the CMRO2 was 116±39 and 111±40 μmol/100 g per minute in the patients and the controls. The BOLD CVR was lower in the ipsilateral than in the contralateral MCA territory of the patients (1.2±0.6 versus 1.6±0.5% per 10 mmHg ΔEtCO2, P < 0.01). Analysis was hampered in three patients due to delayed arrival time. Thus, regional hemodynamic impairment was identified with calibrated MRI. Delayed arrival artifacts limited the interpretation of the images in some patients.

Evaluation of perinatal arterial ischemic stroke using noninvasive arterial spin labeling perfusion MRI

Background:Arterial spin labeling (ASL) magnetic resonance imaging (MRI) can evaluate brain perfusion in neonates noninvasively. The aim of this study was to investigate whether ASL MRI can demonstrate perfusion abnormalities in neonates diagnosed with perinatal arterial ischemic stroke (PAIS).Methods:Pulsed ASL perfusion MR images were acquired in the subacute stage (5–6 d after birth) and at follow-up (13 d to 16 wk after birth) in four PAIS patients. Images were visually evaluated for hypo- and hyperperfusion. In addition, cerebral oxygenation was monitored using near infrared spectroscopy (NIRS).Results:In three PAIS patients, ASL images showed hypoperfusion in the stroke area. In one of these, hyperperfusion was visualized in the periphery of the stroke area. In one PAIS patient, hyperperfusion was seen in the stroke area. In all infants, cerebral oxygenation was higher in the infarcted hemisphere as compared with the contralateral hemisphere. Follow-up ASL images showed partial recovery of perfusion in the stroke area.Conclusion:ASL perfusion MRI is able to reliably detect hypo- and hyperperfusion in PAIS patients and can be used to monitor the evolution of perfusion after an ischemic event.

The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly.

Blood Oxygenation Level Dependent (BOLD) imaging in combination with vasoactive stimuli can be used to probe cerebrovascular reactivity (CVR). Characterizing the healthy, age-related changes in the BOLD-CVR response can provide a reference point from which to distinguish abnormal CVR from the otherwise normal effects of ageing. Using a computer controlled gas delivery system, we examine differences in BOLD-CVR response to progressive hypercapnia between 16 young (28±3years, 9 female) and 30 elderly subjects (66±4years, 13 female). Furthermore, we incorporate baseline T2* information to broaden our interpretation of the BOLD-CVR response. Significant age-related differences were observed. Grey matter CVR at 7mmHg above resting PetCO2 was lower amongst elderly (0.19±0.06%ΔBOLD/mmHg) as compared to young subjects (0.26±0.07%ΔBOLD/mmHg). White matter CVR at 7mmHg above baseline PetCO2 showed no significant difference between young (0.04±0.02%ΔBOLD/mmHg) and elderly subjects (0.05±0.03%ΔBOLD/mmHg). We saw no significant differences in the BOLD signal response to progressive hypercapnia between male and female subjects in either grey or white matter. The observed differences in the healthy BOLD-CVR response could be explained by age-related changes in vascular mechanical properties.

Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI Cerebrovascular Reactivity in Cerebrovascular Disease : A Systematic Review and Meta-Analysis

Background: The cerebrovascular reactivity (CVR) results of blood oxygen level-dependent (BOLD) and arterial spin labeling (ASL) MRI studies performed in patients with cerebrovascular disease (steno-occlusive vascular disease or stroke) were systematically reviewed. Summary: Thirty-one articles were included. Twenty-three (74.2%) studies used BOLD MRI to evaluate the CVR, 4 (12.9%) studies used ASL MRI and 4 (12.9%) studies used both BOLD and ASL MRI. Thirteen studies (3 significant) found a lower BOLD CVR, 2 studies found a similar CVR and 3 studies found a higher CVR in the ipsilateral compared to the contralateral hemisphere. Nine (5 significant) out of 10 studies found a lower BOLD CVR in the ipsilateral hemispheres of patients compared to controls. Six studies (2 significant) found a lower ASL CVR in the ipsilateral compared to the contralateral hemispheres. Three out of 5 studies found a significant lower ASL CVR in the ipsilateral hemispheres of patients compared to controls. Key Messages: This review brings support for a reduced BOLD and ASL CVR in the ipsilateral hemisphere of patients with cerebrovascular disease. We suggest that future studies will be performed in a uniform way so reference values can be established and could be used to guide treatment decisions in patients with cerebrovascular disease.

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery

Background Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. Methods First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. Results First, CT features of the score were circularity (absent, dot(s), <90°, 90–270° or 270–360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. Conclusions The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification.

Brain oxygen saturation assessment in neonates using T2-prepared blood imaging of oxygen saturation and near-infrared spectroscopy.

Although near-infrared spectroscopy is increasingly being used to monitor cerebral oxygenation in neonates, it has a limited penetration depth. The T2-prepared Blood Imaging of Oxygen Saturation (T2-BIOS) magnetic resonance sequence provides an oxygen saturation estimate on a voxel-by-voxel basis, without needing a respiratory calibration experiment. In 15 neonates, oxygen saturation measured by T2-prepared blood imaging of oxygen saturation and near-infrared spectroscopy were compared. In addition, these measures were compared to cerebral blood flow and venous oxygen saturation in the sagittal sinus. A strong linear relation was found between the oxygen saturation measured by magnetic resonance imaging and the oxygen saturation measured by near-infrared spectroscopy (R2 = 0.64, p < 0.001). Strong linear correlations were found between near-infrared spectroscopy oxygen saturation, and magnetic resonance imaging measures of frontal cerebral blood flow, whole brain cerebral blood flow and venous oxygen saturation in the sagittal sinus (R2 = 0.71, 0.50, 0.65; p < 0.01). The oxygen saturation obtained by T2-prepared blood imaging of oxygen saturation correlated with venous oxygen saturation in the sagittal sinus (R2 = 0.49, p = 0.023), but no significant correlations could be demonstrated with frontal and whole brain cerebral blood flow. These results suggest that measuring oxygen saturation by T2-prepared blood imaging of oxygen saturation is feasible, even in neonates. Strong correlations between the various methods work as a cross validation for near-infrared spectroscopy and T2-prepared blood imaging of oxygen saturation, confirming the validity of using of these techniques for determining cerebral oxygenation.

Hippocampal Calcification on Computed Tomography in Relation to Cognitive Decline in Memory Clinic Patients : A Case-Control Study

Background It was recently shown that calcification of the hippocampus can be detected on computed tomography (CT) images and these calcifications occur in up to 20% of people over 50 years of age. However, little is known about hippocampal calcification and its relation to cognition and cognitive decline. Therefore, the aim of this study was to (1) determine the prevalence of hippocampal calcification on CT in memory clinic patients controls, and (2) to assess its relation with cognitive decline. Methods 67 patients from a memory clinic (cases) were matched by age and gender to a control group. In both groups, hippocampal calcification was assessed by two raters on thin slice, non-contrast enhanced brain CT images. Calcifications were scored bilaterally on presence and severity (absent, mild, moderate, severe). Mini Mental State Exam (MMSE) score was determined in cases. Results Hippocampal calcification presence was significantly higher in cases (N = 26, 38.8%) compared to controls (N = 9, 13.4%) (P < .01) with an odds ratio of 4.40 (95%CI: 1.63–14.87). In cases, MMSE score was significantly lower in those with hippocampal calcification compared to those without (21.6 vs 24.5, p = .02). Conclusion In this case-control study we found significantly more hippocampal calcification in patients with cognitive decline as compared to controls. Furthermore, within the cases, MMSE score was significantly lower in those with hippocampal calcification.

Magnetic Resonance Imaging and Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) has improved during the past decades. However, a recent hospital-based study showed that 90-day case fatality is still 30%.1 Determinants of functional outcome after aSAH may include the severity of the initial hemorrhage, rebleeding of the aneurysm, and cerebral ischemia that can be distinguished into (1) acute ischemia at the time of bleeding when intracranial pressure rises and cerebral perfusion pressure drops, (2) procedure-related ischemia from endovascular or neurosurgical treatment of the aneurysm, and (3) delayed cerebral ischemia (DCI), which can occur between days 4 and 14 after the hemorrhage.2,3 Magnetic resonance diffusion weighted imaging (MRI-DWI) is increasingly used for the evaluation of ischemia after aSAH. The aims of the present review were to (1) analyze the proportion of patients with MRI-DWI lesions within 72 hours after aSAH, both before and after aneurysm treatment; (2) study determinants of MRI-DWI lesions within 72 hours after aSAH; (3) analyze the proportion of patients with MRI-DWI lesions between 72 hours and 21 days after aSAH; (4) investigate the predictive value of MRI-DWI lesions within 72 hours for the development of DCI; and 5) investigate whether MRI-DWI can be used for the diagnosis of DCI in patients with clinical deterioration. ### Search Strategy We searched the PUBMED, EMBASE, and Web of Science databases with the following combination of variables: MRI OR magnetic resonance AND subarachnoid hemorrhage OR SAH OR DCI OR delayed cerebral ischemia OR DIND. The last search was performed in June 28, 2016. Only studies published after January 1, 2000, were included to assure a similar degree of image quality, given the technical developments in MRI hardware and sequences. Both prospective and retrospective studies were included. Eligible articles were identified according to the PICO criteria. Type of patient population (P): (1) >95% of patients …