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Erschienen in: Annals of Nuclear Medicine 7/2016

31.05.2016 | Original Article

Cerebral blood flow and metabolism associated with cerebral microbleeds in small vessel disease

verfasst von: Tetsuya Hashimoto, Chiaki Yokota, Kazuhiro Koshino, Ryo Shimomura, Tenyu Hino, Tetsuaki Moriguchi, Yuki Hori, Toshiyuki Uehara, Kazuo Minematsu, Hidehiro Iida, Kazunori Toyoda

Erschienen in: Annals of Nuclear Medicine | Ausgabe 7/2016

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Abstract

Objective

Cerebral microbleeds (CMBs), probably reflecting microangiopathy, have not yet sufficiently been examined in association with cerebral blood flow (CBF) and metabolism. We investigated the relationships between CMBs, and CBF and metabolism in symptomatic small vessel disease.

Methods

We enrolled 22 patients with symptomatic small vessel disease without severe stenosis (>50 %) in major cerebral arteries. Volumes of white matter lesions (WMLs) and number of CMBs were assessed on images of fluid-attenuated inversion recovery and gradient-echo T2*-weighted magnetic resonance imaging, respectively. Patients were divided into two groups according to the median number of CMBs (group I <5, n = 10; group II ≥5, n = 12). Parametric images of CBF, cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction and cerebral blood volume were estimated using positron emission tomography and 15O-labeled gases. The functional values in the cortex–subcortex, basal ganglia, and centrum semiovale were compared between the two groups.

Results

Volumes of WMLs of group II were larger than those of group I (median: 38.4; range: 25.1–91.5 mL vs. median: 11.3; range: 4.2–73.4 mL, p = 0.01). In the centrum semiovale, the mean CBF of group II was significantly lower than that of group I (12.6 ± 2.6 vs. 15.6 ± 3.3 mL/100 g/min, p = 0.04). In the other regions, there were no significant differences in either CBF or CMRO2 between the two groups.

Conclusions

Our study indicated that increases in the number of CMBs with larger volumes of WMLs were associated with cerebral ischemia in the deep white matter in patients with symptomatic small vessel disease.
Literatur
1.
Zurück zum Zitat Roob G, Schmidt R, Kapeller P, Lechner A, Hartung HP, Fazekas F. MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology. 1999;52:991–4.CrossRefPubMed Roob G, Schmidt R, Kapeller P, Lechner A, Hartung HP, Fazekas F. MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology. 1999;52:991–4.CrossRefPubMed
2.
Zurück zum Zitat Jeerakathil T, Wolf PA, Beiser A, Hald JK, Au R, Kase CS, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke. 2004;35:1831–5.CrossRefPubMed Jeerakathil T, Wolf PA, Beiser A, Hald JK, Au R, Kase CS, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke. 2004;35:1831–5.CrossRefPubMed
3.
Zurück zum Zitat Tanaka A, Ueno Y, Nakayama Y, Takano K, Takebayashi S. Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas. Stroke. 1999;30:1637–42.CrossRefPubMed Tanaka A, Ueno Y, Nakayama Y, Takano K, Takebayashi S. Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas. Stroke. 1999;30:1637–42.CrossRefPubMed
4.
Zurück zum Zitat Cordonnier C. Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain. 2007;130:1988–2003.CrossRefPubMed Cordonnier C. Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain. 2007;130:1988–2003.CrossRefPubMed
5.
Zurück zum Zitat Kato H, Izumiyama M, Izumiyama K, Takahashi A, Itoyama Y. Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke. 2002;33:1536–40.CrossRefPubMed Kato H, Izumiyama M, Izumiyama K, Takahashi A, Itoyama Y. Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke. 2002;33:1536–40.CrossRefPubMed
6.
Zurück zum Zitat Fan YH, Mok VC, Lam WW, Hui AC, Wong KS. Cerebral microbleeds and white matter changes in patients hospitalized with lacunar infarcts. J Neurol. 2004;251:537–41.CrossRefPubMed Fan YH, Mok VC, Lam WW, Hui AC, Wong KS. Cerebral microbleeds and white matter changes in patients hospitalized with lacunar infarcts. J Neurol. 2004;251:537–41.CrossRefPubMed
7.
Zurück zum Zitat Prins ND, van Dijk EJ, den Heijer T, Vermeer SE, Jolles J, Koudstaal PJ, et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain. 2005;128:2034–41.CrossRefPubMed Prins ND, van Dijk EJ, den Heijer T, Vermeer SE, Jolles J, Koudstaal PJ, et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain. 2005;128:2034–41.CrossRefPubMed
8.
Zurück zum Zitat Werring DJ, Frazer DW, Coward LJ, Losseff NA, Watt H, Cipolotti L, et al. Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI. Brain. 2004;127:2265–75.CrossRefPubMed Werring DJ, Frazer DW, Coward LJ, Losseff NA, Watt H, Cipolotti L, et al. Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI. Brain. 2004;127:2265–75.CrossRefPubMed
9.
Zurück zum Zitat Poels MM, Ikram MA, van der Lugt A, Hofman A, Niessen WJ, Krestin GP, et al. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology. 2012;78:326–33.CrossRefPubMed Poels MM, Ikram MA, van der Lugt A, Hofman A, Niessen WJ, Krestin GP, et al. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology. 2012;78:326–33.CrossRefPubMed
10.
Zurück zum Zitat Qiu C, Cotch MF, Sigurdsson S, Jonsson PV, Jonsdottir MK, Sveinbjrnsdottir S, et al. Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology. 2010;75:2221–8.CrossRefPubMedPubMedCentral Qiu C, Cotch MF, Sigurdsson S, Jonsson PV, Jonsdottir MK, Sveinbjrnsdottir S, et al. Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology. 2010;75:2221–8.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Patel B, Lawrence AJ, Chung AW, Rich P, Mackinnon AD, Morris RG, et al. Cerebral microbleeds and cognition in patients with symptomatic small vessel disease. Stroke. 2013;44:356–61.CrossRefPubMed Patel B, Lawrence AJ, Chung AW, Rich P, Mackinnon AD, Morris RG, et al. Cerebral microbleeds and cognition in patients with symptomatic small vessel disease. Stroke. 2013;44:356–61.CrossRefPubMed
12.
Zurück zum Zitat Yakushiji Y, Yokota C, Yamada N, Kuroda Y, Minematsu K. Clinical characteristics by topographical distribution of brain microbleeds, with a particular emphasis on diffuse microbleeds. J Stroke Cerebrovasc Dis. 2011;20:214–21.CrossRefPubMed Yakushiji Y, Yokota C, Yamada N, Kuroda Y, Minematsu K. Clinical characteristics by topographical distribution of brain microbleeds, with a particular emphasis on diffuse microbleeds. J Stroke Cerebrovasc Dis. 2011;20:214–21.CrossRefPubMed
13.
Zurück zum Zitat Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology. 2008;70:1208–14.CrossRefPubMed Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology. 2008;70:1208–14.CrossRefPubMed
14.
Zurück zum Zitat Kim KW, Lee DY, Jhoo JH, Youn JC, Suh YJ, Jun YH, et al. Diagnostic accuracy of mini-mental status examination and revised hasegawa dementia scale for Alzheimer’s disease. Dement Geriatr Cogn Disord. 2005;19:324–30.CrossRefPubMed Kim KW, Lee DY, Jhoo JH, Youn JC, Suh YJ, Jun YH, et al. Diagnostic accuracy of mini-mental status examination and revised hasegawa dementia scale for Alzheimer’s disease. Dement Geriatr Cogn Disord. 2005;19:324–30.CrossRefPubMed
15.
Zurück zum Zitat McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34:939–44.CrossRefPubMed McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34:939–44.CrossRefPubMed
16.
Zurück zum Zitat Nezu T, Yokota C, Uehara T, Yamauchi M, Fukushima K, Toyoda K, et al. Preserved acetazolamide reactivity in lacunar patients with severe white-matter lesions: 15O-labeled gas and H2O positron emission tomography studies. J Cereb Blood Flow Metab. 2012;32:844–50.CrossRefPubMedPubMedCentral Nezu T, Yokota C, Uehara T, Yamauchi M, Fukushima K, Toyoda K, et al. Preserved acetazolamide reactivity in lacunar patients with severe white-matter lesions: 15O-labeled gas and H2O positron emission tomography studies. J Cereb Blood Flow Metab. 2012;32:844–50.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Hori Y, Hirano Y, Koshino K, Moriguchi T, Iguchi S, Yamamoto A, et al. Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man. Phys Med Biol. 2014;59:5593–609.CrossRefPubMed Hori Y, Hirano Y, Koshino K, Moriguchi T, Iguchi S, Yamamoto A, et al. Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man. Phys Med Biol. 2014;59:5593–609.CrossRefPubMed
18.
Zurück zum Zitat Kudomi N, Choi E, Yamamoto S, Watabe H, Kim K, Shidahara M, et al. Development of a GSO detector assembly for a continuous blood sampling system. IEEE Trans Nucl Sci. 2003;50:70–3.CrossRef Kudomi N, Choi E, Yamamoto S, Watabe H, Kim K, Shidahara M, et al. Development of a GSO detector assembly for a continuous blood sampling system. IEEE Trans Nucl Sci. 2003;50:70–3.CrossRef
19.
Zurück zum Zitat Kudomi N, Hayashi T, Teramoto N, Watabe H, Kawachi N, Ohta Y, et al. Rapid quantitative measurement of CMRO(2) and CBF by dual administration of (15)O-labeled oxygen and water during a single PET scan-a validation study and error analysis in anesthetized monkeys. J Cereb Blood Flow Metab. 2005;25:1209–24.CrossRefPubMed Kudomi N, Hayashi T, Teramoto N, Watabe H, Kawachi N, Ohta Y, et al. Rapid quantitative measurement of CMRO(2) and CBF by dual administration of (15)O-labeled oxygen and water during a single PET scan-a validation study and error analysis in anesthetized monkeys. J Cereb Blood Flow Metab. 2005;25:1209–24.CrossRefPubMed
20.
Zurück zum Zitat Kudomi N, Watabe H, Hayashi T, Iida H. Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method. Phys Med Biol. 2007;52:1893–908.CrossRefPubMed Kudomi N, Watabe H, Hayashi T, Iida H. Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method. Phys Med Biol. 2007;52:1893–908.CrossRefPubMed
21.
Zurück zum Zitat Yamada S, Saiki M, Satow T, Fukuda A, Ito M, Minami S, et al. Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age. Eur J Neurol. 2012;19:98–104.CrossRefPubMed Yamada S, Saiki M, Satow T, Fukuda A, Ito M, Minami S, et al. Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age. Eur J Neurol. 2012;19:98–104.CrossRefPubMed
22.
Zurück zum Zitat Gao Z, Wang W, Wang Z, Zhao X, Shang Y, Guo Y, et al. Cerebral microbleeds are associated with deep white matter hyperintensities, but only in hypertensive patients. PLoS One. 2014;9:e91637.CrossRefPubMedPubMedCentral Gao Z, Wang W, Wang Z, Zhao X, Shang Y, Guo Y, et al. Cerebral microbleeds are associated with deep white matter hyperintensities, but only in hypertensive patients. PLoS One. 2014;9:e91637.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Schreiber S, Bueche CZ, Garz C, Kropf S, Angenstein F, Goldschmidt J, et al. The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase? J Cereb Blood Flow Metab. 2012;32:278–90.CrossRefPubMed Schreiber S, Bueche CZ, Garz C, Kropf S, Angenstein F, Goldschmidt J, et al. The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase? J Cereb Blood Flow Metab. 2012;32:278–90.CrossRefPubMed
24.
Zurück zum Zitat Conijn MM, Hoogduin JM, van der Graaf Y, Hendrikse J, Luijten PR, Geerlings MI. Microbleeds, lacunar infarcts, white matter lesions and cerebrovascular reactivity—a 7 T study. Neuroimage. 2012;59:950–6.CrossRefPubMed Conijn MM, Hoogduin JM, van der Graaf Y, Hendrikse J, Luijten PR, Geerlings MI. Microbleeds, lacunar infarcts, white matter lesions and cerebrovascular reactivity—a 7 T study. Neuroimage. 2012;59:950–6.CrossRefPubMed
25.
Zurück zum Zitat Gregg NM, Kim AE, Gurol ME, Lopez OL, Aizenstein HJ, Price JC, et al. Incidental cerebral cerebral microbleeds and cerebral blood flow in elderly individuals. JAMA Neurol. 2015;72:1021–8.CrossRefPubMedPubMedCentral Gregg NM, Kim AE, Gurol ME, Lopez OL, Aizenstein HJ, Price JC, et al. Incidental cerebral cerebral microbleeds and cerebral blood flow in elderly individuals. JAMA Neurol. 2015;72:1021–8.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-relatedmicrobleeds. AJNR Am J Neuroradiol. 1999;20:637–42.PubMed Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-relatedmicrobleeds. AJNR Am J Neuroradiol. 1999;20:637–42.PubMed
27.
Zurück zum Zitat Imaizumi T, Horita Y, Hashimoto Y, Niwa J. Dotlike hemosiderin spots on T2*-weighted magnetic resonance imaging as a predictor of stroke recurrence: a prospective study. J Neurosurg. 2004;101:915–20.CrossRefPubMed Imaizumi T, Horita Y, Hashimoto Y, Niwa J. Dotlike hemosiderin spots on T2*-weighted magnetic resonance imaging as a predictor of stroke recurrence: a prospective study. J Neurosurg. 2004;101:915–20.CrossRefPubMed
28.
Zurück zum Zitat Stehling C, Wersching H, Kloska SP, Kirchhof P, Ring J, Nassenstein I, et al. Detection of asymptomatic cerebral microbleeds: a comparative study at 1.5 and 3.0 T. Acad Radiol. 2008;15:895–900.CrossRefPubMed Stehling C, Wersching H, Kloska SP, Kirchhof P, Ring J, Nassenstein I, et al. Detection of asymptomatic cerebral microbleeds: a comparative study at 1.5 and 3.0 T. Acad Radiol. 2008;15:895–900.CrossRefPubMed
29.
Zurück zum Zitat Nandigam RN, Viswanathan A, Delgado P, Skehan ME, Smith EE, Rosand J, et al. MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength. AJNR Am J Neuroradiol. 2009;30:338–43.CrossRefPubMed Nandigam RN, Viswanathan A, Delgado P, Skehan ME, Smith EE, Rosand J, et al. MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength. AJNR Am J Neuroradiol. 2009;30:338–43.CrossRefPubMed
30.
Zurück zum Zitat von Falkenhausen M, Meyer C, Lutterbey G, Morakkabati N, Walter O, Gieseke J, et al. Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T. Eur Radiol. 2007;17:1256–61.CrossRef von Falkenhausen M, Meyer C, Lutterbey G, Morakkabati N, Walter O, Gieseke J, et al. Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T. Eur Radiol. 2007;17:1256–61.CrossRef
31.
Zurück zum Zitat Levin CS. Primer on molecular imaging technology. Eur J Nucl Med Mol Imaging. 2005;32(Suppl 2):S325–45.CrossRefPubMed Levin CS. Primer on molecular imaging technology. Eur J Nucl Med Mol Imaging. 2005;32(Suppl 2):S325–45.CrossRefPubMed
Metadaten
Titel
Cerebral blood flow and metabolism associated with cerebral microbleeds in small vessel disease
verfasst von
Tetsuya Hashimoto
Chiaki Yokota
Kazuhiro Koshino
Ryo Shimomura
Tenyu Hino
Tetsuaki Moriguchi
Yuki Hori
Toshiyuki Uehara
Kazuo Minematsu
Hidehiro Iida
Kazunori Toyoda
Publikationsdatum
31.05.2016
Verlag
Springer Japan
Erschienen in
Annals of Nuclear Medicine / Ausgabe 7/2016
Print ISSN: 0914-7187
Elektronische ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-016-1086-7

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