Nolan S. Hartkamp

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

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.

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.

Validation of planning-free vessel-encoded pseudo-continuous arterial spin labeling MR imaging as territorial-ASL strategy by comparison to super-selective p-CASL MRI.

Vessel‐encoded (VE) pseudo‐continuous arterial spin labeling (p‐CASL) is a territorial ASL (T‐ASL) technique to identify the perfusion territories of cerebral arteries. The aim of this study was to validate the output of three Vessel‐encoded p‐CASL image processing methods, k‐means clustering with and without subsequent linear analysis and a Bayesian framework, by comparison with the perfusion maps acquired with super‐selective p‐CASL.

Vessel-Encoded Arterial Spin Labeling (VE-ASL) Reveals Elevated Flow Territory Asymmetry in Older Adults With Substandard Verbal Memory Performance

To evaluate how flow territory asymmetry and/or the distribution of blood through collateral pathways may adversely affect the brains ability to respond to age‐related changes in brain function. These patterns have been investigated in cerebrovascular disease; however, here we evaluated how flow‐territory asymmetry related to memory generally in older adults.

In vivo visualization of the PICA perfusion territory with super-selective pseudo-continuous arterial spin labeling MRI

In this work a method is described to discern the perfusion territories in the cerebellum that are exclusively supplied by either or both vertebral arteries. In normal vascular anatomy the posterior inferior cerebellar artery (PICA) is supplied exclusively by its ipsilateral vertebral artery. The perfusion territories of the vertebral arteries were determined in 14 healthy subjects by means of a super-selective pseudo-continuous ASL sequence on a 3T MRI scanner. Data is presented to show the feasibility of determining the PICA perfusion territory. In 10 subjects it was possible to accurately determine both PICA perfusion territories. In two subjects it was possible to determine the perfusion territory of one PICA. Examples in which it was not possible to accurately determine the PICA territory are also given. Additionally, the high variability of the extent of the PICA territory is illustrated using a statistical map. The posterior surface of the cerebellum is entirely supplied by the PICA in six subjects. The most posterior part of the superior surface is supplied by the PICA in eight subjects, and the inferior half of the anterior surface in six subjects. The inferior part of the vermis is supplied by the PICA in all subjects. Two subjects were found with interhemispheric blood flow to both tonsils from one PICA without contribution from the contralateral PICA. With the method as presented, clinicians may in the future accurately classify cerebellar infarcts according to affected perfusion territories, which might be helpful in the decision whether a stenosis should be considered symptomatic.

Cerebellar infarct patterns: The SMART-Medea study

Objective Previous studies on cerebellar infarcts have been largely restricted to acute infarcts in patients with clinical symptoms, and cerebellar infarcts have been evaluated with the almost exclusive use of transversal MR images. We aimed to document the occurrence and 3D-imaging patterns of cerebellar infarcts presenting as an incidental finding on MRI. Methods We analysed the 1.5 Tesla MRI, including 3D T1-weighted datasets, of 636 patients (mean age 62 ± 9 years, 81% male) from the SMART-Medea study. Cerebellar infarct analyses included an assessment of size, cavitation and gliosis, of grey and white matter involvement, and of infarct topography. Results One or more cerebellar infarcts (mean 1.97; range 1–11) were detected in 70 out of 636 patients (11%), with a total amount of 138 infarcts identified, 135 of which showed evidence of cavitation. The average mean axial diameter was 7 mm (range 2–54 mm), and 131 infarcts (95%) were smaller than 20 mm. Hundred-thirty-four infarcts (97%) involved the cortex, of which 12 in combination with subcortical white matter. No infarcts were restricted to subcortical branches of white matter. Small cortical infarcts involved the apex of a deep (pattern 1) or shallow fissure (pattern 2), or occurred alongside one (pattern 3) or opposite sides (pattern 4) of a fissure. Most (87%) cerebellar infarcts were situated in the posterior lobe. Conclusions Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.

Distribution of cerebral blood flow in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery stenosis

ObjectiveTo investigate the influence of internal carotid artery (ICA) stenosis on the distribution of blood flow to the caudate nucleus, lentiform nucleus, and thalamus.MethodsWe studied 18 healthy control subjects, 20 patients with a unilateral asymptomatic ICA stenosis, and 15 patients with a recently symptomatic unilateral ICA stenosis. The contribution of the ICAs and the basilar artery to the perfusion of the deep brain structures was assessed by perfusion territory selective arterial spin labeling (ASL) MRI. Differences were tested with a two-tailed Fishers’ exact test.ResultsThe caudate nucleus was predominantly supplied with blood by the ipsilateral ICA in all groups. In 4 of the 15 (27%) the symptomatic patients, the caudate nucleus partially received blood from the contralateral ICA, compared to none of the 18 healthy control subjects (p = 0.03). The lentiform nucleus and the thalamus were predominantly supplied with blood by the ipsilateral ICA and basilar artery respectively in all groups.ConclusionIn patients with a symptomatic ICA stenosis, the caudate nucleus may be supplied with blood by the contralateral ICA more often than in healthy controls.

Time Course of Vascular Reactivity Using Repeated Phase-Contrast MR Angiography in Patients With Carotid Artery Stenosis

Background and Purpose— Cerebral vascular reactivity assessment is typically performed with 2 perfusion measurements before and after a vasodilatory challenge. The aim of this study was to assess the time course of the vasodilatory effect in the brain-feeding arteries after a challenge with acetazolamide in patients with a stenosis of the internal carotid artery (ICA). Methods— Twenty-one patients with a symptomatic ICA stenosis and 18 healthy control subjects underwent 2-dimensional phase-contrast MR angiography to repeatedly measure the blood flow (mL/min) in both ICAs at baseline and in 5-minute intervals for 30 minutes after intravenous administration of acetazolamide. Results— At baseline, the blood flow was significantly lower in the stenosed ICAs of patients (155±17 mL/min) than in the contralateral ICAs (237±21 mL/min, P<0.05) and the ICAs of healthy control subjects (249±15 mL/min, P<0.05) and remained lower throughout the time course. The maximum vasodilatory effect in the stenosed ICAs was observed after 15.3±0.9 minutes, which was significantly later than in the contralateral ICAs (within 12.9±0.7 minutes, P<0.05) and healthy ICAs (within 12.8±0.8 minutes, P<0.05). Conclusions— The onset of the maximum vasodilatory effect after administration of acetazolamide is delayed in patients with a symptomatic ICA stenosis.

Misinterpretation of ischaemic infarct location in relationship to the cerebrovascular territories

Purpose Cerebral perfusion territories are known to vary widely among individuals. This may lead to misinterpretation of the symptomatic artery in patients with ischaemic stroke to a wrong assumption of the underlying aetiology being thromboembolic or hypoperfusion. The aim of the present study was to investigate such potential misinterpretation with territorial arterial spin labelling (T-ASL) by correlating infarct location with imaging of the perfusion territory of the carotid arteries or basilar artery. Materials and methods 223 patients with subacute stroke underwent MRI including structural imaging scans to determine infarct location, time-of-flight MR angiography (MRA) to determine the morphology of the circle of Willis and T-ASL to identify the perfusion territories of the internal carotid arteries, and basilar artery. Infarct location and the perfusion territory of its feeding artery were classified with standard MRI and MRA according to a perfusion atlas, and were compared to the classification made according to T-ASL. Results A total of 149 infarctions were detected in 87 of 223 patients. 15 out of 149 (10%) infarcts were erroneously attributed to a single perfusion territory; these infarcts were partly located in the originally determined perfusion territory but proved to be localised in the border zone with the adjacent perfusion territory instead. 12 out of 149 (8%) infarcts were misclassified with standard assessments and were not located in the original perfusion territory. Conclusions T-ASL with territorial perfusion imaging may provide important additional information for classifying the symptomatic brain-feeding artery when compared to expert evaluation with MRI and MRA.