Regional resting state perfusion variability and delayed cerebrovascular uniform reactivity in subjects with chronic carotid artery stenosis

Arkadiusz Szarmach; Mariusz Kaszubowski; Agnieszka Sabisz; Andrzej F Frydrychowski; Grzegorz Halena; Maciej Piskunowicz; Jaroslaw Dzierzanowski; Michal Studniarek; Edyta Szurowska; Pawel J Winklewski

doi:10.18388/abp.2017_2581

Arkadiusz Szarmach 2nd Department of Radiology, Medical University of Gdansk, Gdańsk, Poland
Mariusz Kaszubowski Department of Economic Sciences, Faculty of Management and Economics, Gdansk University of Technology, Gdańsk, Poland
Agnieszka Sabisz 2nd Department of Radiology, Medical University of Gdansk, Gdańsk, Poland
Andrzej F Frydrychowski Department of Human Physiology, Medical University of Gdansk, Gdańsk, Poland
Grzegorz Halena Department of Cardiovascular Surgery, Medical University of Gdansk, Gdańsk, Poland
Maciej Piskunowicz 1-st Department of Radiology, Medical University of Gdansk, Gdańsk, Poland
Jaroslaw Dzierzanowski Department of Neurosurgery, Medical University of Gdansk, Gdańsk, Poland
Michal Studniarek 1-st Department of Radiology, Medical University of Gdansk, Gdańsk, Poland, Department of Diagnostic Imaging, Medical University of Warsaw, Warsaw, Poland
Edyta Szurowska 2nd Department of Radiology, Medical University of Gdansk, Gdańsk, Poland
Pawel J Winklewski 2nd Department of Radiology, Medical University of Gdansk, Gdańsk, Poland, Department of Human Physiology, Medical University of Gdansk, Gdańsk, Poland, Faculty of Health Sciences, Pomeranian University of Slupsk, Słupsk, Poland

DOI: https://doi.org/10.18388/abp.2017_2581

Abstract

The aim of this study was to assess regional perfusion at baseline and regional cerebrovascular resistance (CVR) to delayed acetazolamide challenge in subjects with chronic carotid artery stenosis.

Sixteen patients (ten males) aged 70.94±7.71 with carotid artery stenosis ≥90% on the ipsilateral side and ≤50% on the contralateral side were enrolled into the study. In all patients, two computed tomography perfusion examinations were carried out; the first was performed before acetazolamide administration and the second 60 minutes after injection.The differences between mean values were examined by paired two-sample t-test and alternative nonparametric Wilcoxon’s test. Normality assumption was examined using W Shapiro-Wilk test.

The lowest resting-state cerebral blood flow (CBF) was observed in white matter (ipsilateral side: 18.4±6.2; contralateral side: 19.3±6.6) and brainstem (ipsilateral side: 27.8±8.5; contralateral side: 29.1±10.8). Grey matter (cerebral cortex) resting state CBF was below the normal value for subjects of this age: frontal lobe – ipsilateral side: 30.4±7.0, contralateral side: 33.7±7.1; parietal lobe – ipsilateral side: 36.4±11.3, contralateral side: 42.7±9.9; temporal lobe – ipsilateral side: 32.5±8.6, contralateral side: 39.4±10.8; occipital lobe – ipsilateral side: 24.0±6.0, contralateral side: 26.4±6.6).

The highest resting state CBF was observed in the insula (ipsilateral side: 49.2±17.4; contralateral side: 55.3±18.4). A relatively high resting state CBF was also recorded in the thalamus (ipsilateral side: 39.7±16.9; contralateral side: 41.7±14.1) and cerebellum (ipsilateral side: 41.4±12.2; contralateral side: 38.1±11.3).

The highest CVR was observed in temporal lobe cortex (ipsilateral side: +27.1%; contralateral side: +26.1%) and cerebellum (ipsilateral side: +27.0%; contralateral side: +34.6%). The lowest CVR was recorded in brain stem (ipsilateral side: +20.2%; contralateral side: +22.2%) and white matter (ipsilateral side: +18.1%; contralateral side: +18.3%). All CBF values were provided in milliliters of blood per minute per 100 g of brain tissue [ml/100g/min].

Resting state circulation in subjects with carotid artery stenosis is low in all analysed structures with the exception of insula and cerebellum. Acetazolamide challenge yields relatively uniform response in both hemispheres in the investigated population.Grey matter is more reactive to acetazolamide challenge than white matter or brainstem.

References

Wintermark M, Reichhart M, Thiran JP, Maeder P, Chalaron M, Schnyder P, Bogousslavsky J, Meuli R. Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients. Ann Neurol. 2002;51:417-32.

MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group. Lancet 1991;337:1235.

North American Symptomatic Carotid Endarterectomy Trial (NASCET) Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis . New Engl J Med. 1991;325:445-453.

Wardlaw JM, Allerhand M, Eadie E, Thomas A, Corley J, Pattie A, Taylor A, Shenkin SD, Cox S, Gow A, Starr JM, Deary IJ. Carotid disease at age 73 and cognitive change from age 70 to 76 years: A longitudinal cohort study. J Cereb Blood Flow Metab. 2016; DOI: 10.1177/0271678X16683693.

Abbott A. Critical Issues That Need to Be Addressed to Improve Outcomes for Patients With Carotid Stenosis. Angiology. 2016;67:420-6.

Frydrychowski AF, Winklewski PJ, Szarmach A, Halena G, Bandurski T. Near-infrared transillumination back scattering sounding--new method to assess brain microcirculation in patients with chronic carotid artery stenosis. PLoS One. 2013;8:e61936.

Szarmach A, Halena G, Kaszubowski M, Piskunowicz M, Szurowska E, Frydrychowski AF, Winklewski PJ. Perfusion computed tomography: 4 cm versus 8 cm coverage size in subjects with chronic carotid artery stenosis. Br J Radiol. 2016;89:20150949.

Szarmach A, Winklewski PJ, Halena G, Kaszubowski M, Dzierżanowski J, Piskunowicz M, Szurowska E, Frydrychowski AF. Morphometric evaluation of the delayed cerebral arteries response to acetazolamide test in patients with chronic carotid artery stenosis using computed tomography angiography. Folia Morphol. 2017;76:10-14.

Szarmach A, Halena G, Kaszubowski M, Piskunowicz M, Studniarek M, Lass P, Szurowska E, Winklewski PJ. Carotid artery stenting and blood–brain barrier permeability in subjects with chronic carotid artery stenosis. Int J Mol Sci. 2017; 18:1008.

Vorstrup S, Brun B, Lassen NA. Evaluation of the cerebral vasodilatory capacity by the acetazolamide test before EC-IC bypass surgery in patients with occlusion of the internal carotid artery. Stroke. 1986;17:1291-8.

Murakami M, Yonehara T, Takaki A, Fujioka S, Hirano T, Ushio Y. Evaluation of delayed appearance of acetazolamide effect in patients with chronic cerebrovascular ischemic disease: feasibility and usefulness of SPECT method using triple injection of ECD. J Nucl Med. 2002;43: 577-83.

Hartkamp NS, Hendrikse J, van der Worp HB, de Borst GJ, Bokkers RP. Time course of vascular reactivity using repeated phase-contrast MR angiography in patients with carotid artery stenosis. Stroke. 2012;43: 553-6.

Vorstrup S, Henriksen L, Paulson OB. Effect of acetazolamide on cerebral blood flow and cerebral metabolic rate for oxygen. J Clin Invest. 1984;74:1634–39.

Hokari M, Kuroda S, Shiga T, Nakayama N, Tamaki N, Iwasaki Y. Combination of a mean transit time measurement with an acetazolamide test increases predictive power to identify elevated oxygen extraction fraction in occlusive carotid artery diseases. J Nucl Med. 2008;49:1922-7.

Chen JJ, Rosas HD, Salat DH. Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage. 2011;55:468-78.

Kudo K, Terae S, Katoh C, Oka M, Shiga T, Tamaki N, Miyasaka K. Quantitative cerebral blood flow measurement with dynamic perfusion CT using the vascular-pixel elimination method: comparison with H2(15)O positron emission tomography. AJNR Am J Neuroradiol. 2003;24:419-26.

Kamano H, Yoshiura T, Hiwatashi A, Abe K, Togao O, Yamashita K, Honda H. Arterial spin labeling in patients with chronic cerebral artery steno-occlusive disease: correlation with (15)O-PET. Acta Radiol. 2013;54:99-106.

Zhang K, Herzog H, Mauler J, Filss C, Okell TW, Kops ER, Tellmann L, Fischer T, Brocke B, Sturm W, Coenen HH, Shah NJ. Comparison of cerebral blood flow acquired by simultaneous [15O]water positron emission tomography and arterial spin labeling magnetic resonance imaging. J Cereb Blood Flow Metab. 2014;34:1373-80.

Matsumoto Y, Ogasawara K, Saito H, Terasaki K, Takahashi Y, Ogasawara Y, Kobayashi M, Yoshida K, Beppu T, Kubo Y, Fujiwara S, Tsushima E, Ogawa A. Detection of misery perfusion in the cerebral hemisphere with chronic unilateral major cerebral artery steno-occlusive disease using crossed cerebellar hypoperfusion: comparison of brain SPECT and PET imaging. Eur J Nucl Med Mol Imaging. 2013;40:1573-81.

Pantano P, Baron JC, Lebrun-Grandié P, Duquesnoy N, Bousser MG, Comar D. Regional cerebral blood flow and oxygen consumption in human aging. Stroke. 1984;15:635-41.

Schumann P, Touzani O, Young AR, Morello R, Baron JC, MacKenzie ET. Evaluation of the ratio of cerebral blood flow to cerebral blood volume as an index of local cerebral perfusion pressure. Brain. 1998;121:1369-79. Erratum in: Brain 1998;121:2027.

Murphy MJ, Tichauer KM, Sun L, Chen X, Lee TY. Mean transit time as an index of cerebral perfusion pressure in experimental systemic hypotension. Physiol Meas. 2011;32:395-405.

Niesen WD, Rosenkranz M, Eckert B, Meissner M, Weiller C, Sliwka U. Hemodynamic changes of the cerebral circulation after stent-protected carotid angioplasty. AJNR Am J Neuroradiol. 2004;25:1162-7.

Trojanowska A, Drop A, Jargiello T, Wojczal J, Szczerbo-Trojanowska M. Changes in cerebral hemodynamics after carotid stenting: evaluation with CT perfusion studies. J Neuroradiol. 2006;33:169-74.

Pikkarainen M, Kauppinen T, Alafuzoff I. Hyperphosphorylated tau in the occipital cortex in aged nondemented subjects. J Neuropathol Exp Neurol. 2009;68:653-60.

Ashraf A, Fan Z, Brooks DJ, Edison P. Cortical hypermetabolism in MCI subjects: a compensatory mechanism? Eur J Nucl Med Mol Imaging. 2015;42:447-58.

Baron JC, Lebrun-Grandie P, Collard P, Crouzel C, Mestelan G, Bousser MG. Noninvasive measurement of blood flow, oxygen consumption, and glucose utilization in the same brain regions in man by positron emission tomography: concise communication. J Nucl Med 1982;23:391–9.

Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M, Leggio MG. The cerebellar cognitive profile. Brain. 2011;134:3672-86.

Van Overwalle F, Heleven E, Ma N, Mariën P. Tell me twice: A multi-study analysis of the functional connectivity between the cerebrum and cerebellum after repeated trait information. Neuroimage. 2017;144:241-252.

Yadav SK, Kumar R, Macey PM, Woo MA, Yan-Go FL, Harper RM. Insular cortex metabolite changes in obstructive sleep apnea. Sleep. 2014;37:951-8.

Sarma MK, Macey PM, Nagarajan R, Aysola R, Harper RM, Thomas MA. Accelerated Echo Planer J-resolved Spectroscopic Imaging of Putamen and Thalamus in Obstructive Sleep Apnea. Sci Rep. 2016;6:31747.

Winklewski PJ, Radkowski M, Wszedybyl-Winklewska M, Demkow U. Brain inflammation and hypertension: the chicken or the egg? J Neuroinflammation. 2015;12:85.

Winklewski PJ, Radkowski M, Demkow U. Neuroinflammatory mechanisms of hypertension: potential therapeutic implications. Curr Opin Nephrol Hypertens. 2016;25:410-6.

Noble J, Jones JG, Davis EJ. Cognitive function during moderate hypoxaemia. Anaesth Intensive Care. 1984;21:180–184.

Sugar O, Gerard RW. Anoxia and brain potentials. J Neurophysiol. 1938;1:558–572.

Barnett HJ. Hemodynamic cerebral ischemia. An appeal for systematic data gathering prior to a new EC/IC trial. Stroke. 1997;28:1857–1860.

Waaijer A, van Leeuwen MS, van Osch MJ, van der Worp BH, Moll FL, Lo RT, Mali WP, Prokop M. Changes in cerebral perfusion after revascularization of symptomatic carotid artery stenosis: CT measurement. Radiology. 2007;245:541-8.

Sato K, Sadamoto T, Hirasawa A, Oue A, Subudhi AW, Miyazawa T, Ogoh S. Differential blood flow responses to CO₂ in human internal and external carotid and vertebral arteries. J Physiol. 2012;590:3277-90.

Skow RJ, MacKay CM, Tymko MM, Willie CK, Smith KJ, Ainslie PN, Day TA. Differential cerebrovascular CO₂ reactivity in anterior and posterior cerebral circulations. Respir Physiol Neurobiol. 2013;189:76-86.

Mandell DM, Han JS, Poublanc J, Crawley AP, Kassner A, Fisher JA, Mikulis DJ. Selective reduction of blood flow to white matter during hypercapnia corresponds with leukoaraiosis. Stroke. 2008;39:1993-8.

Bhogal AA, Siero JC, Fisher JA, Froeling M, Luijten P, Philippens M, Hoogduin H. Investigating the non-linearity of the BOLD cerebrovascular reactivity response to targeted hypo/hypercapnia at 7T. Neuroimage. 2014;98:296-305.

Bhogal AA, Philippens ME, Siero JC, Fisher JA, Petersen ET, Luijten PR, Hoogduin H. Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7T. Neuroimage. 2015;114:239-48.

Bhogal AA, De Vis JB, Siero JC, Petersen ET, Luijten PR, Hendrikse J, Philippens ME, Hoogduin H. The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly. Neuroimage. 2016;139:94-102.

Ito H, Kanno I, Ibaraki M, Hatazawa J. Effect of aging on cerebral vascular response to PaCo2 changes in humans as measured by positron emission tomography. J Cereb Blood Flow Metab. 2002;22:997-1003.

Nöth U, Kotajima F, Deichmann R, Turner R, Corfield DR. Mapping of the cerebral vascular response to hypoxia and hypercapnia using quantitative perfusion MRI at 3 T. NMR Biomed. 2008;21:464-72.

Campbell BC, Christensen S, Levi CR, Desmond PM, Donnan GA, Davis SM, Parsons MW. Comparison of computed tomography perfusion and magnetic resonance imaging perfusion-diffusion mismatch in ischemic stroke. Stroke. 2012;43:2648-53.

Kudo K, Sasaki M, Yamada K, Momoshima S, Utsunomiya H, Shirato H, Ogasawara K. Differences in CT perfusion maps generated by different commercial software: quantitative analysis by using identical source data of acute stroke patients. Radiology 2010; 254:200–9.

Kamalian S, Kamalian S, Maas MB, Goldmacher GV, Payabvash S, Akbar A, Schaefer PW, Furie KL, Gonzalez RG, Lev MH. CT cerebral blood flow maps optimally correlate with admission diffusion-weighted imaging in acute stroke but thresholds vary by postprocessing platform. Stroke. 2011;42:1923-8.