AGE-RELATED CEREBRAL VENTRICULAR VOLUME CHANGES IN HEALTHY ELDERLY HUMANS

AGE-RELATED CEREBRAL VENTRICULAR VOLUME

CHANGES IN HEALTHY ELDERLY HUMANS

ALTERAÇÕES VOLUMÉTRICAS DOS VENTRÍCULOS CEREBRAIS

RELACIONADAS A IDADE EM IDOSOS SAUDÁVEIS

Mário Luciano de Mélo Silva Júnior1,2_{, Paula Rejane Beserra Diniz}1,3_{, Daniella Araújo de Oliveira}1,4_{, Luciana Patrizia Alves de}

Andrade Valença1,2,5_{, Antonio Carlos dos Santos}6_{, Marcelo Moraes Valença}1,5

ABSTRACT

Introduction: Normal aging is associated with morphological

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Keywords: EUDLQ DWURSK\ WKLUG YHQWULFOH IRXUWK YHQWULFOH DJLQJ

magnetic resonance imaging

RESUMO

Introdução: O envelhecimento normal está associado a alterações

morfológicas do cérebro. O sistema ventricular está localizado pro- IXQGDPHQWHQRHQF«IDORHUHȵHWHRSURFHVVRJOREDOGHDWURȴDGRSD-rênquima. Uma vez que doenças neurodegenerativas cursam com dilatação mais proeminente dos ventrículos cerebrais, estabelecer SDU¤PHWURVYROXP«WULFRVGHQRUPDOLGDGHHPQRVVDSRSXOD©¥RLGRVD saudável se faz necessário, podendo ser uma ferramenta a mais para diferenciar o normal do patológico. Objetivo: Investigar alterações volumétricas dos ventrículos cerebrais em brasileiros idosos sau-dáveis. Métodos: (VWXGR WUDQVYHUVDO FRP LPDJHQV GH UHVVRQ¤QFLD PDJQ«WLFD7GRHQF«IDORGHLGRVRVVDXG£YHLVsDQRV PXOKHUHV2VGDGRVIRUDPH[DPLQDGRVSRUW«FQLFDVGHVHJPHQWD-ção manual. As regiões de interesse foram os ventrículos cerebrais HRYROXPHLQWUDFUDQLDQR&ULDPRVRVVXEJUXSRVΖGRVRVDQRV H0DLVLGRVRV!DQRVSDUDDDQ£OLVHResultados: O volume de WRGRVRVYHQWU¯FXORVDXPHQWRXFRPDLGDGHSFRPH[FH©¥R do quarto ventrículo. O terceiro e os ventrículos laterais aumentaram HYH]HVUHVSHFWLYDPHQWHHQWUHRVJUXSRV2YROXPHYHQWUL-FXODUP«GLRIRLGHsGRYROXPHLQWUDFUDQLDQRQRVΖGRVRVH GHsQRVPDLVLGRVRVRTXHUHSUHVHQWDsPOHsPO respectivamente. Observamos correlação positiva de moderada a forte entre volume ventricular e idade, com a melhor correlação no WHUFHLURYHQWU¯FXORU 2YROXPHLQWUDFUDQLDQRGLPLQXLFRPD LGDGHVHPVLJQLȴF¤QFLDHVWDW¯VWLFDConclusão: os ventrículos cere-EUDLVDXPHQWDPVLJQLȴFDWLYDPHQWHFRPRHQYHOKHFLPHQWRHPLGRVRV saudáveis, exceto o quarto ventrículo.

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INTRODUCTION

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METHODS

Volunteers

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Magnetic resonance imaging

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Manual segmentation process and anatomical

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Statistical analysis

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Ethical aspects

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RESULTS

Reliability

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Total intracranial volume

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Lateral ventricles

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Third ventricle

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Fourth ventricle

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Table 1 – Linear regression and correlation of corrected volume vs. age

Variable

Lateral

Third Fourth TVV Left Right Both

Linear regression Slope F 15.2 16.5 14.5 26.9 0.9 16.7 p .001 < .001 .001 < .001 .369 < .001 r² .444 .465 .434 .587 .043 .468 Correlation r .542 .612 .559 .710 .207 .596 p .011 .003 .008 < .001 .369 .004 r = Spearman. For Fourth ventricle, Pearson correlation was used. TVV = total ventricular volume.

Table 2 – Linear regression and correlation of absolute volume vs. age

Variable

Lateral

Third Fourth TVV Left Right Both

Linear regression Slope F 13.1 15.5 14.5 19.7 0.3 14.7 p .001 < .001 .001 < .001 .569 .001 r² .408 .449 .434 .509 .017 .437 Correlation r .479 .579 .559 .651 .132 .566 p .030 .006 .008 .001 .569 .007 r = Spearman. For Fourth ventricle, Pearson correlation was used. TVV = total ventricular volume.

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Total ventricular volume

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DISCUSSION

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Group

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Third Fourth TVV Left Right Both

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CONCLUSIONS

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Figure 1. Linear regressions of both lateral, third and fourth ventricles and total ventricular volumes. ICV = intracranial volume.

Table 4 – Ventricular volumes (absolute in ml and corrected in %) in different studies Reference n Age Techinique TVV CVV Amarki et al. 2010 46 71.0±6.0 RM 3.0 T – Manual 37.0±18.0 2.5±1.2 Blatter et al., 1995* 15 59.8±2.2 RM 1.5 T – Manual 24.2±12.2 – Matsumae et al., 1996 22 72.0±5.0 RM 1.5 T – Semiautomatic 33.0±10.0 2.4±0.6 Carmichael et al., 2010# 52 83.6±4.4 RM 1.5 T – Automatic 30.7±12.6 – Resnick et al., 2000 63 64.6±3.2 RM 1.5 T - Semiautomatic 25.2±10.8 – This study 21 67.7±6.3 RM 1.5 T - Manual 22.1±17.3 1.8±1.4 TVV = total ventricular volume; CVV = corrected ventricular volume. *Only women data were used. #_{Prospectively healthy subjects.}

ACKNOWLEDGMENTS

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REFERENCES

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