Effects of Acute Dehydration on Brain Morphology in Healthy Humans

Transcription

1 Human Bain Mapping 30: (2009) Effects of Acute Dehydation on Bain Mophology in Healthy Humans Matthew J. Kempton, 1,2 * Ulich Ettinge, 1 Anne Schmechtig, 1 Edwad M. Winte, 3 Luke Smith, 4 Tey McMois, 4 Iain D. Wilkinson, 5 Steven C.R. Williams, 1 and Macus S. Smith 4 1 Cente fo Neuoimaging Sciences, Institute of Psychiaty, King s College London, London, United Kingdom 2 Section of Neuobiology of Psychosis, Institute of Psychiaty, King s College London, London, United Kingdom 3 The Cente fo Spot and Execise Science, Sheffield Hallam Univesity, Sheffield, United Kingdom 4 School of Spot, Execise and Health Sciences, Univesity of Chicheste, Chicheste, United Kingdom 5 Academic Unit of Radiology, Univesity of Sheffield, Sheffield, United Kingdom Abstact: Dehydation can affect bain stuctue which has impotant implications fo human health. In this study, we measued egional changes in bain stuctue following acute dehydation. Healthy voluntees eceived a stuctual MRI scan befoe and afte an intensive 90-min themal-execise dehydation potocol. We used two techniques to detemine changes in bain stuctue: a manual point counting technique using MEASURE, and a fully automated voxelwise analysis using SIENA. Afte the execise egime, paticipants lost (2.2% 6 0.5%) of thei body mass. Using SIENA, we detected expansion of the venticula system with the lagest change occuing in the left lateal venticle (P coected fo multiple compaisons) but no change in total bain volume (P ). Using manual point counting, we could not detect any change in venticula o bain volume, but thee was a significant coelation between loss in body mass and thid venticula volume incease ( , P ). These esults show venticula expansion occus following acute dehydation, and suggest that automated longitudinal voxelwise analysis methods such as SIENA ae moe sensitive to egional changes in bain volume ove time compaed with a manual point counting technique. Hum Bain Mapp 30: , VC 2007 Wiley-Liss, Inc. Key wods: dehydation; magnetic esonance imaging; stuctual anatomy INTRODUCTION *Coespondence to: D. Matthew J. Kempton, Cente fo Neuoimaging Sciences, PO89, Institute of Psychiaty, DeCespigny Pak, London SE5 8AF, United Kingdom. matthew.kempton@iop.kcl.ac.uk Received fo publication 3 August 2007; Revised 17 Septembe 2007; Accepted 18 Septembe 2007 DOI: /hbm Published online 6 Decembe 2007 in Wiley InteScience (www. intescience.wiley.com). Human suvival is associated with an ability to maintain homeostasis though peseving fluid balance and egulating body coe tempeatue [Adolph, 1947]. Homeostasis is challenged on a daily basis though a combination of voluntay, i.e. physical activity, involuntay, i.e. illness, and envionmental factos, i.e. heat and humidity [Amstong, 2000]. An incease in coe tempeatue and paallel decease in body fluid esults in impaied cadiovascula function [Costill et al., 1976; Haison, 1985; Nadel et al., 1980] and physical pefomance [Amstong et al., 1985; VC 2007 Wiley-Liss, Inc.

2 Kempton et al. Calliste et al., 1991; Hickne et al., 1991; Hoffman et al., 1995]. Peseving fluid balance, while optimizing physical pefomance, is of consideable inteest to athletes. Given the danges associated with dysegulated fluid balance, fluid eplacement ecommendations have been developed fo athletes fo the peiods befoe, duing and afte physical activity [Gisolfi and Duchman, 1992; Maughan and Noakes, 1991]. Despite this, weight-classified athletes have been epoted to employ active and passive fluid loss methods immediately befoe competing to enable them to compete in weight categoies >5% below thei usual weight. This is based on the belief that this appoach will povide a psychological and physiological advantage ove fellow competitos [Fogelholm, 1994; Smith, 2006]. If changes in bain stuctue such as shinkage occu following dehydation, thee ae impotant implications fo spoting events such as boxing whee dehydation might incease the likelihood of bain damage afte blows to the head [Canall and Waden, 1995; Dickson et al., 2005]. Few studies have investigated the effects of dehydation on human bain stuctue. An ealy X-ay computed tomogaphy (CT) study suggested a decease in venticula size following dehydation [Mellanby and Reveley, 1982], although the authos caution against dawing conclusions fom the study as it was based on a single paticipant. A ecent magnetic esonance imaging (MRI) study has shown that dehydation due to esticted fluid intake ove a 16-h peiod leads to eduction in total bain volume, an effect that can be evesed following acute ehydation [Duning et al., 2005]. A futhe study showed that inceases in venticula volume following physical execise coelated with eductions in body mass [Dickson et al., 2005]. In the pesent study, we attempt to map the egional changes in bain mophology on a voxel-by-voxel basis in addition to global volume changes following acute dehydation. We acquied stuctual MRI scans befoe and afte igoous execise and applied two complementay image analysis techniques: steeology, which is widely used and povides an unbiased estimate of the volume of an object [Robets et al., 2000]; and stuctual image evaluation, using nomalization of atophy (SIENA), which is a completely automated analysis designed fo detecting bain atophy in longitudinal studies [Smith et al., 2002]. Taking into consideation pevious evidence, we hypothesized that acute dehydation would lead to a eduction in bain volume and subtle egional changes in bain mophology such as venticula expansion. MATERIALS AND METHODS Paticipants Seven male voluntees ecuited fom spot and execise science students at the Univesity of Chicheste took pat in the study (physical chaacteistics: mean 6 SD, age yeas, body mass kg, and height m). All paticipants undetook egula physical activity but wee naïve to methods of acute dehydation. All paticipants gave witten infomed consent afte being made awae of the possible isks and discomfot of the expeimental pocedues. Paticipants also completed a Health Histoy Questionnaie to assess thei suitability fo undegoing MRI scanning. Ethics appoval was obtained fom the ethics committee at the Institute of Psychiaty and Maudsley Hospital, London. Pocedue Duing the 24-h peiod befoe the study paticipants wee instucted not to paticipate in stenuous activity, and to maintain a nomal diet and avoid alcohol consumption. Paticipants consumed 500 ml of wate duing the evening befoe epoting to the laboatoy the following moning. On aival at the laboatoy [tempeatue 20 (6 1)8C, elative humidity (45% 6 5%)] paticipants consumed a futhe 500 ml of wate, 1 h befoe physical execise. Paticipants wee asked to uinate and nude body mass was detemined (Avey scales, Bimingham, England). Each paticipant then eceived a baseline bain MRI scan befoe the dehydation potocol. Dehydation Potocol A themal-execise dehydation potocol was devised to decease body mass by 2 3% in 90-min [Smith, 1998]. The themal component equied paticipants to wea thee layes of clothing: Laye 1 consisted of a modified black bin line (Sainsbuy s, UK) fitted next to the paticipants skin; Laye 2 was a chemical wafae potective suit that compised a hooded impemeable plastic top and bottoms (Royal Navy, Ministy of Defence, UK); and Laye 3 was a spots tacksuit that compised a cotton top and bottoms (Adidas, Gemany). The thee layes wee won thoughout the 90-min themal-execise potocol. The execise component was divided into thee phases. Phase 1 equied paticipants to cycle on a Monak E824E egomete (Monak, Sweden) at 130 W fo 50 min. Phase 2 was a 10-min seated ecovey. Phase 3 equied 30 min cycling at 130 W. Heat ate was monitoed thoughout the 90-min themal-execise potocol to assess execise intensity and themal load (Pola PE 3000, Kempele, Finland). On completion of the themal-execise potocol, paticipants wee eweighed and pecentage change in body mass was detemined. Paticipants wee given a 15-min supine ecovey peiod befoe completing a post dehydation bain MRI scan. MRI Scanning MRI scanning was pefomed on a 1.5 Tesla GE Signa MRI scanne (Geneal Electic, Milwaukee, WI). Images wee acquied in the coonal plane using a thee dimensional, T 1 weighted, invesion-ecovey pepaed, steady 292

3 Acute Dehydation and Bain Mophology state, spoiled gadient-echo sequence (TR ms, TE 5 2 ms, TI ms, flip angle 5 208, slice thickness mm, matix size , voxel dimensions mm 3, NEX 5 1). Assessment of Bain Volume Change Using SIENA SIENA vesion 2.4, pat of FSL (FMRIB Softwae Libay, was used to detemine the pecentage change in global bain volume fo each paticipant afte acute dehydation, and voxelwise statistics wee used to eveal egional changes in bain mophology. SIENA is a fully automated analysis tool designed fo detecting small changes in bain mophology ove time and is insensitive to diffeent scanning paametes [Smith, 2002]. Pevious eseach has shown SIENA to have geate sensitivity in detecting longitudinal changes in bain stuctue compaed with semiautomated outlining methods [Andeson et al., 2007]. In addition, it has been shown to be highly epoducible, with an eo of less than 0.15% in bain volume when healthy contols wee scanned on two occasions unde identical conditions [Smith et al., 2002]. SIENA has been used in a numbe of studies investigating changes in bain stuctue [Batsch et al., 2007; Mezzapesa et al., 2007; Petes et al., 2006] and is biefly descibed below. The SIENA pogam is applied to each paticipant s pai of images, scanned befoe and afte acute dehydation. The bain and skull ae extacted fom each pai [Smith et al., 2002], and the two bain images ae aligned to each othe, using the skull images to constain the scaling of the alignment [Jenkinson et al., 2002; Jenkinson and Smith, 2001]. The aligned images ae then esampled into a thee-dimensional space which is halfway between the two images to ensue the same intepolation has been applied to each image. The bain images ae then segmented to find bain/nonbain edge points [Zhang et al., 2001]. At each edge point a pependicula line is dawn though the bain suface, and the pesegmented image is sampled along the line to find the steepest intensity gadient, thus accuately making the edge of the bain in each image. Finally, the mean displacement of bain suface at each edge point is conveted to a global pecentage change in bain volume. To allow voxelwise statistical inteogation of the data, the mean displacement images fo each paticipant ae dilated (14 times using a kenel, nonbinay dilation) and tansfomed into Monteal Neuological Institute (MNI) space and masked by a standad bain edge image [Batsch et al., 2007]. The numbe of dilations pefomed is the standad numbe fo a SIENA voxelwise analysis and povides a lage enough band of flow values aound the bain-csf bounday so that the standad bain edge mask can extact values fo each point on the mask. The esultant images ae then smoothed by a Gaussian kenel of half width 10 mm fo statistical analysis. A one-sample t-test was used to detemine if thee was significant change in global bain volume (SPSS Inc., Chicago, IL. vesion 15). Voxelwise one-sample t-tests wee pefomed on the smoothed dilated displacement images using SPM5 (Wellcome Depatment of Imaging Neuoscience) basic models to highlight egions whee thee was displacement of bain suface, thus indicating egional changes in bain volume. To investigate the elationship between displacement and loss in body mass, we used a simple linea egession model in SPM5. Assessment of Whole-Bain and CSF Volume Change Using MEASURE Stuctual MRI scans wee analyzed fo the estimation of whole-bain and venticula volumes using a manual egions-of-inteest (ROI) appoach. ROI analysis was undetaken on the basis of steeological pinciples implemented in PC-based softwae (MEASURE) [Bata et al., 1997]. MEASURE supeimposes a gid on the image and allows the use to view voxels in thee mutually othogonal planes. Gid points falling within an a pioi defined anatomic egion of inteest ae manually maked by a ate. Head tilt was coected in all bains befoe measuements to align images along the anteio commissue posteio commissue (AC-PC) line and the intehemispheic fissue. A gid setting of was used fo wholebain volume, whee one gid point equals one image voxel. Fo the much smalle stuctues of the thid and lateal venticles a maximally detailed gid setting of was applied to impove measuement accuacy [Dickson et al., 2003]. All stuctues wee analyzed by the same ate (AS) and wee individually confimed by a second ate (UE). The anatomic definition of whole-bain volume was based on peviously descibed boundaies [Ettinge et al., 2007; Schulze et al., 2003]. Whole-bain volume included all gid points falling within cotical and subcotical gay matte, white matte, and the bain stem supeio to the pons. Any CSF within these boundaies, ceebellum, optic chiasm, pineal and pituitay glands, dua mate, supeio sagittal, staight and tansvese sinuses wee excluded. Inte-ate eliability (ates AS and UE) was high, Intaclass coelation coefficient (ICC) The technical eo of measuement (TEM) [Goe and Austalian Spots, 2000] was 34.4 cm 3 (3.1%), confiming good eliability of atings by the two ates. Inta-ate eliability (AS) was high: ICC , TEM cm 3 (1.8%). Both lateal and thid venticula CSF is clealy visible in MRI scans. The demacations of lateal [DeLisi et al., 1995] and thid [Fannon et al., 2000] venticles wee as follows. The lateal venticle measuement included CSF fom the entie lateal venticula system including the tempoal hon. The lateal venticle was bodeed anteioly by fontal cotex, medially by the septum pellucidum, intaventicula foamen and copus callosum and posteioly by the occipital cotex. Inte-ate eliability was high: 293

4 Kempton et al. ICC , TEM cm 3 (5.1%). Inta-ate eliability was high: ICC , TEM cm 3 (4.3%). Measuements of the thid venticle included CSF that was bodeed by the anteio commissue, the fonix, the stia medullais, the pineal body, the supeio and infeio colliculi, the midbain and mamillay body, the thalamus, and hypothalamus. Inte-ate eliability was high: ICC , TEM cm 3 (5.1%). Inta-ate eliability was high: ICC , TEM cm 3 (1.7%). Statistical analysis of whole-bain and venticula volumes was caied out in SPSS Vesion 15 (SPSS, Chicago, IL.). To investigate effects of dehydation, we fist compaed egional volumes measued befoe and afte execise using paied samples t-tests (sepaately fo whole-bain, lateal, and thid venticle). Effect sizes wee calculated using the fomula (Vol 1 2 Vol 2 )/SD Voldiff whee Vol 1 is the volume at fist scan, Vol 2 is the volume at second scan, and SD Voldiff is the standad deviation of the diffeence scoe (Vol 1 2 Vol 2 ). To exploe elationships between dehydation effects and egional bain volumes, Peason coelation coefficients wee calculated between pecentage changes both in egional volume and body mass, fo each anatomical vaiable. We then caied out a least-poducts egession analysis [Ludbook, 1997] to investigate both systematic as well as andom change ove the two scans. In all cases, statistical significance was taken to be P < RESULTS Change in Body Mass All paticipants completed the test pocedues and no modeate o sevee symptoms of discomfots wee epoted. Body mass deceased fom kg befoe dehydation to kg afte dehydation (t , P < 0.001). This equated to (2.19% %) loss in body mass. Change in Bain Volume (SIENA) Fom the SIENA global bain volume analysis, thee was no eduction in global bain volume afte acute dehydation (P , mean change in bain volume %, SD %), see Figue 1. Howeve fom the SIENA voxelwise analysis thee was expansion of the venticula system afte acute dehydation, see Figue 2. The most extensive expansion occued in the left lateal venticle (Z 5 5.4, P coected fo multiple compaisons, Monteal Neuological Institute (MNI) coodinates x 5222, y 5226, z 5 18, mean displacement mm, SD mm). No coelation of venticula expansion and body weight loss passing the P < 0.05 coected theshold was found using the SIENA voxelwise analysis. Figue 1. Global pecentage change in bain volume afte acute dehydation measued by SIENA, n 5 7. Individual paticipants ae shown on the left and the mean and standad deviation of the goup is shown on the ight. Change in Bain and Venticula Volumes (MEASURE) Desciptive statistics and effect sizes of whole-bain and venticula volumes befoe and afte execise ae pesented in Table I. Thee wee no changes as a esult of dehydation fo any of the stuctues evaluated hee (Table II). All effect sizes wee in the small ange [Cohen, 1988]. Least poducts egession (LPR) indicated that thee was only vey small systematic change in volume acoss scans and low andom change, i.e. no oveall diffeences and good stability in volumes fom befoe to afte dehydation. Pecentage body mass change was positively coelated with pecentage change in thid venticle volume ( , P ), indicating that loss in body mass was associated with geate thid venticula enlagements (Fig. 3). Change in body mass was negatively coelated with pecentage change in bain volume ( , P ), indicating that geate body mass loss was associated with geate bain volume eductions (Fig. 3). Thee was no coelation between changes in body mass and lateal venticle volume (P ). DISCUSSION The pesent study employed a igoous themal-execise potocol to achieve acute dehydation in healthy individuals. The themal-execise potocol has peviously been vali- 294

5 Acute Dehydation and Bain Mophology Figue 2. Regional changes in bain volume afte acute dehydation measued by SIENA. Coloed egions indicate volume loss at a P < uncoected voxel-level theshold (Z > 3.1). Regions whee colo gaduates to white indicate volume loss at P < 0.05 coected voxel-level theshold (Z > 4.7). dated in expeimental studies of spots medicine [Smith et al., 2000]. In ou study, 90 min of themal-execise led to a (2.2% 6 0.5%) loss of body mass, suppoting the validity of the dehydation method employed hee. The study s aim was to identify the effects of acute dehydation on bain mophology in healthy humans. To povide an analysis of changes in bain mophology, we used two complementay image analysis methods that investigated goss anatomical changes in bain volume and venticles: a steeological egion-of-inteest (ROI) method (MEASURE) and a moe detailed voxel-by-voxel analysis (SIENA). Bain Changes Following Dehydation The SIENA analysis evealed expansion of the left lateal venticle and suggested expansion of the ight lateal, thid, and fouth venticle afte dehydation (the latte esults not passing coection fo multiple compaisons). No expansion of CSF filled spaces adjacent to the inteio suface of the skull was found. Although the mean displacement of the venticle wall was small, and eflects the TABLE I. Desciptive statistics fo whole-bain and venticula volumes (MEASURE) Befoe dehydation Afte dehydation Effect size Whole-bain 1104 (74) 1104 (75) Thid venticle 0.55 (0.24) 0.57 (0.23) Lateal venticle 13.3 (8.0) 14.6 (10.1) All volumes ae given as means (standad deviations) in cm 3. Whole-bain volume compises gey and white matte. The sample size fo all vaiables is N 5 7. sensitivity of SIENA to subvoxel changes [Smith et al., 2002], a displacement of this magnitude ove the entie suface of the venticles would lead to a moe appeciable change in total venticula volume. Dehydation inceases the osmolality of extacellula fluid in the body and deceases blood volume [Costill et al., 1976]. Both ae pocesses that could educe total bain volume and lead to a coesponding incease in CSF volume. Inceased concentations of solutes in extacellula fluid cause wate to move fom inside cells to the extacellula fluid along the osmotic gadient, causing cellula shinkage [Gullans and Vebalis, 1993]. Howeve, cells pevent lage inceases and deceases in volume by actively egulating thei intacellula solute (paticulaly potassium ions), which is of vital impotance in the bain because of the fixed volume of the canium [Sticke and Vebalis, 2003]. Indeed, if such homeostatic pocesses wee not TABLE II. Statistical analysis of whole-bain and venticula volumes (MEASURE) t-test Whole-bain t , P Thid venticle t , P Lateal venticle t , P LPR Value of Loss Function LPR Paametes a b a 1.70E b c LPR, least poducts egession. a Optimal solution found afte 1 iteation. b Optimal solution found afte 5 iteations. c Optimal solution found afte 8 iteations. The sample size fo all analyses is N

6 Kempton et al. Figue 3. Relationship between change in body weight and anatomical volumes (MEASURE). The left panel shows the elationship between pecentage change in body mass and thid venticle volume. The ight panel shows the elationship between pecentage change in body mass and whole-bain volume. SEE, Standad Eo of the Estimate. active we might expect to see lage changes in bain stuctue following dehydation. As bain volume deceases, the empty space is filled by CSF; this may come fom an incease in poduction o a decease in absoption of CSF, o fom the CSF filled spinal dual sack which unlike the canium, can change its volume in esponse to intacanial pessue [Lee et al., 2001; Lofgen and Zwetnow, 1973]. The ROI analysis using MEASURE did not identify any diffeences in thid o lateal venticula volume following dehydation. The failue to obseve such an effect using the ROI method might be because it fails to conside subsections of the stuctues studied. A pevious study using a manual ROI segmentation of the venticles also did not find a systematic effect of dehydation on oveall volume [Dickson et al., 2005]. Howeve, both the pesent study and Dickson et al. [2005] obseved a elationship between change in body mass and venticula enlagement. While Dickson et al. [2005] studied the venticula system without distinguishing between thid and lateal venticles, ou study indicates that the finding might be specific to the thid venticle. The obseved elationship indicates that geate loss in body mass was associated with geate thid venticle enlagement. As in the study by Dickson et al. [2005], we obseved that small eductions in body mass afte dehydation (<2%) wee paadoxically associated with deceased venticle volume, while lage body mass eductions (>2.5%) wee associated with venticula enlagement. Additionally, we obseved a elationship between changes in body mass and bain volume (assessed using MEASURE). This elationship indicated that geate body weight loss was associated with geate bain volume eductions. Howeve, thee was no evidence of changes in oveall bain volume fom befoe to afte dehydation. This obsevation was made using both the manual ROI analysis (MEASURE) and the fully automated analysis (SIENA). This esult is in contast with a pevious study that epoted eductions in bain volume following dehydation [Duning et al., 2005]. Diffeences in study potocols could account fo the discepancy. Fo example, while we used an acute, 90-min themal-execise method to achieve dehydation, Dunning et al. [2005] esticted fluid intake in thei paticipants fo 16 h. Moeove, we had fewe paticipants than Dunning et al. [2005] and hence, could have been undepoweed to detect the eduction in total bain volume. The failue of ou study to detect changes in bain volume but to detect venticula expansion, suggests that the latte measue may be moe sensitive to dehydation. Limitations A limitation of this study is that only seven paticipants wee included, futue studies with a lage numbe of subjects may be able to detect changes in total bain volume and moe extensive changes in venticula system. All the paticipants in this study wee young, healthy males which may limit the extapolation of ou findings to the geneal population. Futhemoe, the SIENA analysis is esticted to displacement of the bain bounday and it is possible that this analysis may have missed changes in volume of stuctues within the bain. Voxel-based mophomety is anothe technique which could have been applied to the data to detect egional changes. Likewise the MEASURE analysis was esticted to the whole bain volume, lateal venticles, and thid venticle and may have missed othe egional changes. Although the 296

7 Acute Dehydation and Bain Mophology MEASURE inta-ate eliability was high, the small vaiability between measues may have masked the even smalle effect of dehydation. Implications The cuent finding of subtle inceases in venticula volume afte dehydation has seveal implications: fist, the incease in venticula volume may be impotant fo athletes who use acute dehydation egimes and compete in contact weight-classified spots such as boxing and matial ats. Inceased CSF volume could allow the bain to move futhe in the canium following a blow to the head, thus inceasing deceleation foces as the bain impacts into the canium. Such apid deceleation of the bain can cause contusion injuies [Besenski, 2002]. Second, abnomal fluid intake occus in neuopsychiatic conditions and may thus affect the measuement of bain volumes in these patient populations. Fo example, while polydipsia is obseved in some cases of psychosis [McKinley et al., 2004], patients with dementia often display symptoms of dehydation because of pooly maintained fluid intake. The pesent findings and those of pevious studies [Dickson et al., 2005; Duning et al., 2005] thus have clinical as well as scientific implications. Clinically, abnomal egulation of fluid intake may advesely affect bain stuctue and function and should thus be ecognized at an ealy stage. Scientifically, goup diffeences in level of dehydation may intoduce eo in compaisons of bain volumes. Howeve, it should be noted that the dehydation effects obseved hee ae elatively small compaed with goup diffeences seen in the psychiatic liteatue [Wight et al., 2000]. Futue Wok If neuons ae foced to incease intacellula solutes duing dehydation to maintain thei volume, one might anticipate this pocess to affect thei function. Accodingly, it would be useful to assess the effects of dehydation on bain function via functional MRI. It would also be impotant to obseve egional changes in bain stuctue following ehydation to veify that the obseved lateal venticle expansion is evesed. In addition, it would be of inteest to ty and sepaate the effects of dehydation (inceased extacellula osmolality and deceased plasma volume) on bain stuctue by scanning voluntees befoe and afte inceased salt intake o blood donation, espectively. CONCLUSIONS Oveall, the pesent study eveals venticula expansion following acute dehydation, a finding which may have implications fo athletes of weight-classified spots. Dehydation effects on bain stuctue ae of a small magnitude and ae bette detected with automated pocesses such as SIENA compaed with point-counting techniques. ACKNOWLEDGMENTS The authos acknowledge the suppot povided to Luke Smith duing his MSc in Spots Science fom Mancheste Metopolitan Univesity. 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