Background: There is an unmet need for screening methods to detect and quantify cerebral small vessel disease (SVD). Transcranial Doppler ultrasound (TCD) flow spectra of the larger intracranial arteries probably contain relevant information about the microcirculation. However, it has not yet been possible to exploit this information as a valuable biomarker. Methods: We developed a technique to generate normalized and averaged flow spectra during middle cerebral artery Doppler ultrasound examinations. Second, acceleration curves were calculated, and the absolute amount of the maximum positive and negative acceleration was calculated. Findings were termed ‘TCD-profiling coefficient' (TPC). Validation study: we applied this noninvasive method to 5 young adults for reproducibility. Degenerative microangiopathy study: we also tested this new technique in 30 elderly subjects: 15 free of symptoms but with MRI-verified presence of cerebral SVD, and 15 healthy controls. SVD severity was graded according to a predefined score. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) study: TPC values of 10 CADASIL patients were compared with those of 10 healthy controls. Pulse wave analysis and local measurements of carotid stiffness were also performed. CADASIL patients were tested for cognitive impairment with the Montreal Cognitive Assessment scale. White matter and basal ganglia lesions in their cerebral MRI were evaluated according to the Wahlund score. Results: Validation study: the technique delivered reproducible results. Degenerative microangiopathy study: patients with SVD had significantly larger TPCs compared with controls (SVD: 2,132; IQR 1,960-2,343 %/s vs. controls: 1,935; IQR 1,782-2,050 %/s, p = 0.01). TPC values of subjects with SVD significantly correlated with SVD severity scores (R = 0.58, n = 15, p < 0.05). CADASIL study: TPC values of CADASIL patients were significantly higher than values of the controls (CADASIL: 2,504; IQR 2,308-2,930 %/s vs. controls 2,084; 1,839-2,241 %/s, p = 0.008), and also significantly higher than the TPC values of the patients with SVD from the degenerative microangiopathy study (p = 0.007). CADASIL patients had significantly worse cognitive test results than healthy controls. Conclusion: TCD-profiling detects impairment of the cerebral microcirculatory state. The suitability of the TCD-profiling for the evaluation of cerebral microangiopathy was confirmed.

Keywords:
AVERAGE, Cerebral small vessel disease, Transcranial Doppler ultrasound, CADASIL
1.
Patton N, Aslam T, Macgillivray T, Pattie A, Deary IJ, Dhillon B: Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat 2005;206:319-348.
2.
Faraci FM, Heistad DD: Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol Rev 1998;78:53-97.
3.
Launer LJ, Berger K, Breteler MM, Dufouil C, Fuhrer R, Giampaoli S, Nilsson LG, Pajak A, de Ridder M, van Dijk EJ, Sans S, Schmidt R, Hofman A: Regional variability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE). Neuroepidemiology 2006;26:23-29.
4.
Patel B, Markus HS: Magnetic resonance imaging in cerebral small vessel disease and its use as a surrogate disease marker. Int J Stroke 2011;6:47-59.
5.
Lee KY, Sohn YH, Baik JS, Kim GW, Kim JS: Arterial pulsatility as an index of cerebral microangiopathy in diabetes. Stroke 2000;31:1111-1115.
6.
Terborg C, Gora F, Weiller C, Rother J: Reduced vasomotor reactivity in cerebral microangiopathy: a study with near-infrared spectroscopy and transcranial Doppler sonography. Stroke 2000;31:924-929.
7.
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-Invasive Investigation of Large Arteries: Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588-2605.
8.
Deppe M, Knecht S, Henningsen H, Ringelstein EB: AVERAGE: a Windows program for automated analysis of event related cerebral blood flow. J Neurosci Methods 1997;75:147-154.
9.
Leute A, Kirchhof P, Breithardt G, Goette A, Lewalter T, Meinertz T, Oeff M, Ravens U, Steinbeck G, Weiss T: [German Competence Network on Atrial Fibrillation (AFNET). A nationwide cooperation for better research and patient care]. Med Klin (Munich) 2006;101:662-666.
10.
Knecht S, Oelschlager C, Duning T, Lohmann H, Albers J, Stehling C, Heindel W, Breithardt G, Berger K, Ringelstein EB, Kirchhof P, Wersching H: Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy. Eur Heart J 2008;29:2125-2132.
11.
Lonie JA, Tierney KM, Ebmeier KP: Screening for mild cognitive impairment: a systematic review. Int J Geriatr Psychiatry 2009;24:902-915.
12.
Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M, Wallin A, Ader H, Leys D, Pantoni L, Pasquier F, Erkinjuntti T, Scheltens P; European Task Force on Age-Related White Matter Changes: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001;32:1318-1322.
13.
Widder B, Paulat K, Hackspacher J, Mayr E: Transcranial Doppler CO2 test for the detection of hemodynamically critical carotid artery stenoses and occlusions. Eur Arch Psychiatry Neurol Sci 1986;236:162-168.
14.
Markus HS, Harrison MJ: Estimation of cerebrovascular reactivity using transcranial Doppler, including the use of breath-holding as the vasodilatory stimulus. Stroke 1992;23:668-673.
15.
Mok V, Ding D, Fu J, Xiong Y, Chu WW, Wang D, Abrigo JM, Yang J, Wong A, Zhao Q, Guo Q, Hong Z, Wong KS: Transcranial Doppler ultrasound for screening cerebral small vessel disease: a community study. Stroke 2012;43:2791-2793.
16.
Xiong Y, Mok V, Wong A, Chen X, Chu WC, Fan Y, Soo Y, Wong KS: The age-related white matter changes scale correlates with cognitive impairment. Eur J Neurol 2010;17:1451-1456.
17.
Birns J, Jarosz J, Markus HS, Kalra L: Cerebrovascular reactivity and dynamic autoregulation in ischaemic subcortical white matter disease. J Neurol Neurosurg Psychiatry 2009;80:1093-1098.
18.
Kollar J, Schulte-Altedorneburg G, Sikula J, Fulesdi B, Ringelstein EB, Mehta V, Csiba L, Droste DW: Image quality of the temporal bone window examined by transcranial Doppler sonography and correlation with postmortem computed tomography measurements. Cerebrovasc Dis 2004;17:61-65.
19.
Lorenz MW, Loesel N, Thoelen N, Gonzalez M, Lienerth C, Dvorak F, Rolz W, Humpich M, Sitzer M: Effects of poor bone window on the assessment of cerebral autoregulation with transcranial Doppler sonography - a source of systematic bias and strategies to avoid it. J Neurol Sci 2009;283:49-56.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.