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Analysis of cerebrovascular watershed areas in patients with high-grade carotid artery stenosis using DSC-based time-to-peak maps
Vanessa Griese1, Stephan Kaczmarz1, Anne Kluge1,2, Kim van de Ven3, Michael Helle4, Hendrik Kooijman-Kurfuerst4, Claus Zimmer1, Christian Sorg 1,5, Jens Göttler1, and Christine Preibisch1,5,6

1Neuroradiology, Technical University of Munich, Munich, Germany, 2Radioonkology and Radiotherapy, Charité Berlin, Berlin, Germany, 3Philips Healthcare, Best, Netherlands, 4Philips Research, Hamburg, Germany, 5TUM Neuroimaging Center (TUM-NIC), Technical University of Munich, Munich, Germany, 6Neurology, Technical University of Munich, Munich, Germany

Synopsis

Internal carotid artery stenosis (ICAS) is one of the leading causes for thromboembolic and hemodynamic cerebral infarction. Here, we present data from an ongoing clinical MRI-study in patients with asymptomatic, high-grade ICAS and healthy controls. Our major aim was to establish a method to delineate individual watershed areas in patients and controls using MRI-based dynamic susceptibility contrast (DSC) time-to-peak (TTP) maps, also including the anatomical information of magnetic resonance angiography (MRA) to define individual vascular territories. Watershed areas were enlarged and shifted in many of the vascular territories of stenosed carotid arteries, being verified by ss-pCASL in a subgroup.

Purpose

High-grade internal carotid artery stenosis (ICAS) accounts for approximately 20% of ischemic strokes due to thromboembolism and hemodynamic infarction in cerebral watershed areas.1 These most vulnerable areas are located between intracranial vessel territories, where arterial blood supply is physiologically compromised.2,3 Patients showing good collateralization via the Circle of Willis (CoW) often remain asymptomatic and have a lower risk for cerebral infarction.5 Analyzing the impact of ICAS on these watershed areas, we previously used non-individualized watershed masks based on the standard anatomy of vascular territories to analyse cerebral perfusion in ICAS (Fig.3C).6 However, the individual variants of the CoW and the relative enlargement and displacement of watershed areas in chronic hypoperfusive states produced inconclusive results.2,6 Therefore, the aim of this study was to manually define individualized watershed masks based on dynamic susceptibility contrast (DSC)-derived time-to-peak (TTP) maps accounting for the individual vascular anatomy of the CoW.

Methods

In this ongoing clinical study, we enrolled to date 23 patients (70.5±6.8y, 15 males) with unilateral ICAS (>70% according to the NASCET criteria), and 29 healthy controls (70.3±4.7y, 13 males), who underwent an MRI examination on a clinical 3T Ingenia MR-Scanner (Philips Healthcare, Best, Netherlands). A 16-channel head-coil was used for acquisition of pseudo-continuous arterial spin labeling (pCASL) data (background suppression, label duration=1800ms, post label delay=2000ms, segmented 3D-GRASE readout, 3 repetitions including M0, TE=7.4ms, TR=4403ms, voxel size 2.7x2.9x6mm3, 16 slices). Afterwards, we conducted a contrast enhanced magnetic resonance angiography (MRA) of the neck (17ml Gd-DTPA) and obtained DSC-data during a bolus injection of 15ml Gd-DTPA (flow 4 ml/s) using single-shot GE-EPI (TR=1516ms, TE=30ms, α=60°, 80 repetitions). Data evaluation used custom programs in MATLAB (MathWorks) and SPM12 (http://www.fil.ion.ucl.ac.uk/spm/). Evaluation of pCASL followed recent recommendations of the ISMRM perfusion study group and DSC data were processed as described previously.7,8 TTP maps derived from slice-timing corrected DSC data served as a reference for contour forming of watershed masks using a visually defined reasonable binary threshold in Vinci (http://www.nf.mpg.de/vinci3/). The initial masks included venous blood flow and the ventricular system, which had to be excluded manually (Fig.1). Other parts of the masks required extrapolating extension, since they did not reach into grey matter. The individual anatomy of the CoW was assessed via MRA, which guided the splitting into left and right vascular territories of the bilateral carotid arteries (Fig.2). In a subgroup of patients, we additionally used superselective-pCASL (ss-pCASL) to visualize the individual vascular perfusion territories for verification of the masks (Fig.2).9 For evaluation of cerebral hypoperfusion, masks were used to extract mean pCASL-based CBF values (Fig.4).

Results

Watershed areas could well be delineated on TTP maps. Considering variations of the CoW, MRA-imaging enabled a correlation between brain tissue and vascular territories. Additionally, ss-pCASL, available in a subgroup of patients, proofed expected individual collateralizations and allowed an even more precise delineation of individual perfusion territories (Fig.2). In contrast to healthy controls, watershed area masks of our patients showed a lateralization with enlarged masks on the affected hemisphere (Fig.1). A VOI evaluation of pCASL-based CBF maps using the watershed area masks demonstrated symmetric perfusion in healthy controls, while patients showed reduced perfusion on the affected hemisphere (Fig.4).

Discussion

These preliminary results of individualized, manually defined masks of watershed areas based on DSC-derived TTP maps are promising. We could clearly demonstrate lateralization of perfusion impairment in patients with unilateral ICAS, which was not observed using non-individualized masks based on common vascular anatomy.6 Manual delineation of individualized watershed masks revealed large deviations from standard vascular anatomy in many patients, demonstrating the importance of taking into account individual variants of the vascular territories when comparing perfusion between hemispheres. In the literature, TTP is considered a very sensitive parameter to estimate impaired perfusion and might serve as a diagnostic and prognostic tool to delineate areas of higher risk for hemodynamic infarction.10, 11

Acknowledgements

The authors acknowledge the financial support by the Leonhard-Lorenz Stiftung.

References

1. Petty GW, Brown RD, Whisnant JP, Sicks JD, O’Fallon WM & Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke, 30:2513-2516. (1999)

2: Momjian-Major MD, Baron MD, FRCP, FMedSci, The Pathophysiology of Watershed Infarction in Internal Carotid Artery Disease. Stroke, 36:567-577(2005).

3. Mangla et al., Border Zone Infarcts: Pathophysiology and Imaging Characteristics. RadioGrapphics, 31:1201–1214 (2011).

4. Jian-wei Ni, Hiroyuki Ohta, Kinzo Matsumoto, Hiroshi Watanabe. Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Research, 653(1-2):231-236. (1994)

5. Schaller. Imaging of Carotid Artery Stenosis. Springer, p.157. (2007)

6. Kaczmarz et al. Evaluation of perfusion and hypoxia parameters in healthy subjects and patients with high-grade carotid artery stenosis, Proc. Intl. Soc. Mag. Reson. Med. 24. Abstract 4383. (2016)

7.Alsop DC, Detre JA, Golay X, Günther M, Hendrikse J, Hernandez-Garcia L, Lu H, MacIntosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2015 Jan; 73(1):102-16. (Epub 2014)

8.Kluge A, Lukas M, Toth V, Pyka T, Zimmer C, Preibisch C. Analysis of three leakage-correction methods for DSC-based measurement of relative cerebral blood volume with respect to heterogeneity in human gliomas. Magn Reson Imaging. 34(4):410-21. (2016)

9. Helle M, Norris DG, Rüfer S, Alfke K, Jansen O, van Osch MJ. Superselective pseudocontinuous arterial spin labeling. Magn Reson Med.; 64(3): 777-786 (2010)

10. Sobesky et al. Which Time-to-Peak Threshold Best Identifies Penumbral Flow? A Comparison of Perfusion-Weighted Magnetic Resonance Imaging and Positron Emission Tomography in Acute Ischemic Stroke. Stroke. (2004)

11. Salvolini, Scarabino. High Field Brain MRI. p.96-98. (2006)

Figures

Fig.1: Watershed-mask definition in a patient with right-sided ICAS. TTP map with threshold contour at 8.5 sec shows clear lateralisation of perfusion impairment (A). Resulting individualized watershed-masks for the left (blue) and right hemisphere (red) demonstrate enlarged ipsilateral border zones. This example also illustrates that manual correction is necessary to exclude venous influences (arrows) and the ventricular system (star).

Fig.2: Exemplary patient, presenting a variant of the CoW and accordingly deviating perfusion territories. MRA (A) and TOF (B) show a single A1-segment of the anterior cerebral artery (Azygos-ACA) originating from the right ICA. Due to the incomplete CoW, the ACA-territory is only supplied from the right ICA bilateraly. Incidental finding of an intracranial aneurysm (star) at the anterior communicating artery. Extracranial stenosis of the right ICA (arrow). ss-pCASL reveals the corresponding vascular perfusion territories. In the differentiation between left (C) and right (D) vascular blood supply this patient shows a visible shift of perfusion territories.

Fig.3: Creation of watershed-masks based on TTP and vascular territories: A) TTP-map with a threshold contour at 8.0sec. B) Individualized watershed-mask (green) based on threshold contour in TTP. Comparison between standardized masks (C) obtained by our previous method and individualized masks (D) of watershed areas. Left and right blood supply is shown in blue and red, respectively. The individualized masks (D) match the information concerning vascular anatomy we received from MRA and ss-pCASL in the same patient (Fig.2).

Fig.4: VOI evaluation of pCASL-based CBF maps using the watershed-area masks being additionally restricted to grey matter. Right vascular territory values are depicted in red, left in blue. Patients with unilateral stenosis of the right (A) and left (B) internal carotid artery (ICA) show a clear lateralization in CBF matching the affected vascular territory, while healthy controls (C) present a symmetrical perfusion.

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)
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