Effect of Fat: Assessment of Apparent Diffusion Coefficient

Effect of Fat: Assessment of Apparent Diffusion Coefficient Abstract Objectives: Recent studies have indicated that excessive fat may confound assessment of diffusion in organs with high fat content, such as the liver and breast. However, the extent of this effect in the kidney, which is not considered a major fat deposition site, remains unclear. This study tested the hypothesis that renal fat may impact DWI parameters, and proposes a three-compartment model (TCM) to circumvent this effect. Methods: Using computer simulations, we investigated the effect of fat on assessment of apparent diffusion coefficient (ADC), intravoxel incoherent-motion (IVIM) and TCM-derived pure-diffusivity. In domestic pigs fed a high-cholesterol (Obese) or normal diet (Lean) (n=7 each), DWI parameters were calculated using IVIM and correlated to renal histology. IVIM-derived pure diffusivity was also compared among 15 essential hypertension (EH) patients classified by BMI (high vs. normal). Finally, pure diffusivity was calculated and compared in 8 patients with atherosclerotic renal artery stenosis (ARAS) and 5 healthy subjects using IVIM and TCM. Results: Simulations showed that unaccounted fat results in the underestimation of intravoxel incoherent-motion (IVIM)-derived pure-diffusivity, particularly at lower fat contents. Moreover, TCM, which incorporates highly diffusion-weighted images (b>2500s/mm2), could correct for fat-dependent underestimation. Animal studies confirmed lower ADC and pure-diffusivity in Obese vs. Lean pigs with otherwise healthy kidneys. Similarly, EH patients with high BMI had lower ADC (1.9 vs. 2.110-3 mm2/s) and pure-diffusivity (1.7 vs. 1.910-3mm2/s) than those with normal BMI.   Pure-diffusivity calculated using IVIM was not different between the ARAS and healthy subjects, but TCM revealed significantly lower diffusivity in ARAS. Conclusions: Excessive renal fat may cause underestimation of renal ADC and pure-diffusivity, which may hinder detection of renal pathology. Models accounting for fat contribution may help reduce the variability of diffusivity calculated using DWI. Keywords: Renal adiposity, Diffusion-weighted imaging, intravoxel incoherent motion, obesity.   Ã‚   Over the past two decades, diffusion-weighted imaging (DWI) has evolved to an important tool for studying neurological disorders (1-3), while application of this method for characterization of abdominal pathological conditions awaited improved hardware and robust pulse sequences over nearly a decade (4). In the kidney, DWI has been used to investigate chronic kidney disease (CKD) (5), renal lesions (6), and deteriorating allografts (7). Nevertheless, the contribution of tubular flow and hemodynamics to the apparent diffusion constant (ADC), the diffusion quantitative index of the single compartment mono-exponential model, complicates tissue characterization and renal DWI analysis (8). This encouraged implementation of models incorporating a larger number of compartments to differentiate pure diffusion from pseudo-diffusive components. Indeed, in the kidney the intra-voxel incoherent motion (IVIM) analytical method, which utilizes a two-compartment model associated with pure diffusion and flow, showed superiority over the mono-exponential decay model (9, 10). However, recent studies on hepatic DWI identified fat as a potential third compartment with a significant confounding effect (11, 12), even in non-steatotic livers (13, 14) or other organs (15). Abdominal DWI is typically performed using an echo-planar imaging (EPI) readout, which uses a water-only excitation. Selected excitation or fat suppression methods prevent contribution of the fat signal associated with peaks spectrally distant from water, but cannot effectively eliminate the signal from fat components with resonance frequencies close to water proton frequency. For instance, peaks between 4.2-5.3 ppm associated with triglycerides, which account for nearly 8.7% of the total in vivo fat content, remain unsuppressed (11). Moreover, in the kidney, which is located in the vicinity of bowel, susceptibility artifacts may significantly reduce the efficacy of spectral fat suppression. Because the diffusion constant of lipid molecules is orders of magnitude smaller than that in water an d remains nearly unattenuated over the conventional range of b-values, the amplitude of the fat signal, especially at high b-values, can be prominent compared to the attenuated water signal (16), and therefore has a considerable impact on DWI parameters assessment (17). The epidemic of obesity stresses the importance of characterization of the effect of ectopic fat on DWI parameters, particularly in subjects with high body mass index (BMI). Increased renal adiposity (18, 19) may potentially interfere with interpretation of DWI in the kidney in obese subjects, but to date this effect has not been evaluated. The aim of this study was to explore the effect of renal fat accumulation and suboptimal suppression on DWI parameters. We investigated this effect using computer simulations and verified the error in a large animal model of obesity, and in healthy subjects and in the presence of renal pathological conditions in humans. We hypothesized that residual MR signal from fat causes underestimation of renal ADC and IVIM pure-diffusivity, the magnitude of which may approximate a reduction in these parameters elicited by renal pathology. Moreover, we suggest that the fat-dependency of DWI parameters may be corrected by estimating the MR signal of excessive fat using heavily diffusion-weighted images. Assuming that an unattenuated fat signal acts as an independent compartment, we formulated our model by adding a third exponential decay term to the bi-exponential IVIM model to account for the contribution of fat: (1) In our notation, C and are the fractions of extravascular water and fat in the DWI signal intensity. Dfast, Dslow, andDfat are diffusion coefficients for extravascular water (pure-diffusivity), intravascular flow-dependent component (pseudo-diffusion), and fat, respectively. The product of the fat diffusion coefficient and the b-values, over the conventional range of b-values is small such that the exponential part of the third term can be approximated by one. This simplifies the last term in Equation (1) to a constant signal offset as follows: (2) Considering that at higher b-values (~1000 s/mm2) conventionally used in DWI, the water-component of the signal intensity decays to nearly a few percent of its value at b0 (b=0 s/mm2), while the fat-related fraction (FRF), f, remains nearly unattenuated over the imaging b-value spectrum, the magnitude of FRF and its impact on calculated DWI parameters becomes significant. I. Simulations Simulations in this study pursued four aims. First, to show that in the absence of fat signal, the three-compartment model (TCM) reduces to IVIM. This would essentially verify that a non-zero FRF is not merely a result of overfitting the data of an intrinsically two-compartment system into a three-compartment model, and in fact represents a third independent compartment. Second, to investigate the influence of FRF, as illustrated in equation (1), on the diffusion parameters calculated using the bi-exponential IVIM model. Third, to examine the effect of signal-to-noise ratio (SNR) on the accuracy of DWI parameters assessed using IVIM and TCM, particularly since increasing the degrees of freedom in TCM per se reduces the stability of the regularization methods. Finally, to test if in the presence of fat signal the DWI parameters calculated using IVIM and TCM would be b-value dependent. We simulated the total MR signal using the TCM, including fast and slow decays associated with intra- and extravascular fluid, as well as the FRF signal as a third compartment. Simulations were performed for diffusion parameters similar to DWI values reported for the kidney (10), over a range of FRFs (0-10%) and SNRs (2.5-50dB) (Table 1). IVIM and TCM were used to extract DWI parameters. In TCM, the total MR signal intensity for all b-values was subtracted by the signal intensity from the corresponding voxel of the high b-value (>2500 s/mm2) image, and the data were then fitted to a bi-exponential model. Table 1 shows the values used in the simulations. To verify the b-value dependency, DWI parameters were calculated from a set of b-values with the highest value being either 600, 1000, or 2000 s/mm2. II. Animal study All animal procedures followed the Guideline for the Care and Use of Laboratory Animals (National Research Council, National Academy Press, Washington, DC, 1996) and were approved by the Institutional Animal Care and Use Committee at Mayo Clinic. Fourteen domestic swine in this study were fed ad lib for 16 weeks. Seven animals consumed a normal diet (Controls) and the other half (Obese) a high fat/carbohydrate diet (5B4L; Purina Test Diet, Richmond, IN) containing (in % kcal) 17% protein, 20% complex carbohydrates, 20% fructose, and 43% fat and supplemented with 2% cholesterol and 0.7% sodium cholate. We have recently shown that this diet induces obesity and adiposity (20). Diffusion-weighted MRI scans were performed at the completion of diet. Renal volume and hemodynamics were assessed 2-3 days apart from MR scans, using multi-detector computed tomography (MDCT). Prior to each in vivo study animals were anesthetized (Telazol 5mg/kg and xylazine 2mg/kg in saline), and anesthesia maintained with intravenous ketamine (0.2 mg/kg/min) and xylazine (0.03 mg/kg/min) (for CT), or inhaled 1-2% isoflurane (for MRI) throughout the course of imaging. Blood pressure was measured using an arterial catheter during the MDCT scanning session. Animals were injected with 10cc of heparin and euthanized with a lethal intravenous dose of sodium pentobarbital (100 mg/kg) a few days after the in vivo studies. Then the kidneys were removed and immersed in saline containing heparin. The tissue was stored at -80 °C or preserved in formalin for histology. a. Diffusion-weighted Imaging (DWI) DWI was performed on a 3T scanner (GE Medical Systems, Milwaukee, Wisconsin) using a torso array coil. Images were collected using a single-shot echo-planar sequence with bipolar gradient. In all animals, 4-6 coronal slices in oblique planes were collected for b-values 50, 100, 200, 300, 600, 800 and 1000 s/mm2. MR parameters were set to TR/TE 1800/79ms, field of view 35cm, Bandwidth 648Hz/pixel, Number of averages 3, slice thickness 2.5mm, and matrix size 128128. All acquisitions were performed during suspended respiration. b. MDCT imaging Renal hemodynamics were assessed from contrast-enhanced MDCT images, as previously detailed (21). A pigtail catheter was advanced through the left jugular vein to the superior vena cava to inject contrast media during the scan. Then animals were moved to MDCT unit (Somatom Sensation 64; Siemens Medical Solutions, Forchheim, Germany). Following localization of the kidneys, a bolus of iopamidol (0.5 ml/kg over 2s) was injected, and after a 3-second delay, 140 consecutive scans were acquired over approximately 3 minutes. After the flow scan and an additional contrast injection, a volume study was performed. Axial images were acquired at helical acquisition with thickness of 0.6mm and resolution of 512512, and reconstructed at 5mm thickness. c. Lipid Panel Lipid (total cholesterol, triglyceride, high density lipid (HDL)) was measured (Roche) at the Mayo Immunochemical Core Laboratory from blood samples, and low-density lipid (LDL) was calculated. d. Morphological Studies Images were acquired using an ApoTome microscope (Carl ZEISS SMT, Oberkochen, Germany). Renal fibrosis was quantified by colorimetric measurements in 5 µm slides stained for trichrome. Tubular dilation was measured in Periodic acid-Schiff (PAS)-stained slides counterstained with Hemotoxylin. Intracellular lipid accumulation was assessed by colorimetric measurements in Oil-Red-O stained slides from frozen tissue counterstained with Hematoxylin. III. Human study The study was approved by the Institutional Review Board of the Mayo Clinic, in accordance with the Declaration of Helsinki and the Health Insurance Portability and Accountability Act (HIPAA) guidelines. All patients provided written informed consent before enrollment. Fifteen patients with essential hypertension (EH) were recruited from an on-going study, to study the effect of renal fat on DWI parameters. Patients were divided in two groups based on their BMI: an obese group (n=10, BMI≠¥30kg/m2) and a lean group (n=5, BMI 20-25kg/m2). Additionally, diffusion parameters assessments in healthy vs. impaired (post-stenotic) kidneys, with and without fat correction, were compared in eight patients with atherosclerotic renal artery stenosis (ARAS), and five healthy controls. a. DWI In patients 3-8 axial images were acquired on 3T scanner (GE Medical Systems, Milwaukee, WI and Siemens Medical Systems, Erlangen, Germany) with MR parameters TR/TE, Bandwidth, Slice thickness, matrix size, and b-values were set to 2000-2400/60-94ms, 1953 Hz/pixel, 7mm, 128128 or 160160, and 100, 300, 600, 900 (s/mm2) in the first study with EH patients. In ARAS and Control subjects the TR/TE were 2600-4286/59-112ms. Pure-diffusivity was calculated from b-values ≠¥300 s/mm2 and fat-related fraction was assessed from high b-values, 2000-2500 s/mm2. b. Clinical parameters and Lipid Panel Clinical and laboratory parameters including age, sex, weight, BMI, blood pressure, serum creatinine, estimated glomerular filtration rate (eGFR), and lipid panel levels were evaluated at study entry by standard procedures. IV. Data analysis a. DWI Pixel-by-pixel maps of quantitative indices of mono-exponential model, ADC, and bi- and tri-exponential models, IVIM and TCM parameters, respectively, were generated (Figure 1), as shown previously (22). The threshold for fast vs. slow components was set to 300s/mm2 in both animal and patient studies (23). Large cortical regions of interest (ROIs) were drawn on b0 DWI images and transferred to the maps as detailed before (22). Mean values of ADC and IVIM parameters were calculated by averaging values in all corresponding ROIs for all slices in the subject. b. MDCT Using contrast-enhanced MDCT in animals, single-kidney volume, GFR, perfusion, and renal blood flow (RBF) were calculated. To calculate renal function and hemodynamics, the cortical and medullary signal attenuation vs. time curves were fitted to an extended Γ-variate model. Regional blood volumes and mean transit times were calculated to estimate cortical and medullary perfusion and blood flows (products of perfusion and the corresponding volumes). Total RBF was assessed as the sum of cortical and medullary flows. Finally, GFR was evaluated using the slope of the cortical proximal tubular curve, as previously shown (21). Data Analysis software All analyses were performed in MATLAB ® (MathWork, Natick, MA, USA) and Analyzeâ„ ¢ (Biomedical Imaging Resource, Mayo Clinic, MN, USA). V. Statistical Analysis Simulation results are shown as mean  ± STD, and in vivo results as Median [First Quartile Third Quartile]. Minimum sample size was calculated using power analysis for minimum power value of 0.8. Non-parametric Mann-Whitney was used for comparison among groups. For p values

Effect of injection or Suction and Magnetic Field on oscillatory flow i

An oscillatory hydrodynamic flow through porous medium bounded by two horizontal parallel porous plates in the presence of transverse magnetic field is investigated. Both the stationary plates are subjected to the same constant injection / suction velocities ( V ). A closed form analytical solution is obtained and the affects of different parameters (Injection / suction Parameter, Darcy number, Hartmann number, Frequency of oscillations etc.) on velocity field and skin-friction are discussed with the help of graphs in details. Key words: Oscillatory flow, Magnetic field, Injection / suction, Planner channel. 1 Introduction: The flows of fluids through porous media have attracted the attention of a number of scholars because of their possible applications in many branches of science and technology. In fact a porous material containing the fluid is a non-homogeneous medium but it may be possible to treat it as a homogeneous one, for the sake of analysis, by taking its dynamical properties to be equal to the averages of the original non-homogeneous continuum. Thus a complicated problem of the flow through a porous medium gets reduced to the flow problem of a homogeneous fluid with some additional resistance. The hydrodynamic channel flow is a classical problem for which exact solution can be obtained Schillicting [1]. Eckert [2] obtained the exact solution of Navier-Stokes equations for the flow between two parallel porous plates with constant injection/suction. In view of numerous important engineering and geophysical applications of the channel flows through porous medium, for example in the fields of chemical engineering for filtration and purification processes, in the fields of agriculture engineering f... ...Sci. Acad. 75(1) (2009): 41-48. 14 Garg, B.P., Singh, K.D. and Pathak, Reena (2011). An analysis of radiative, free-convective and mass transfer flow past an accelerated vertical plate in the presence of transverse magnetic field, J. Rajasthan Acad. Phy. Sci. 10(1) (in press). 15 Moreau, R. â€Å"MagnetoHydrodynamics†. Kluwer Academic Publishers, Dordrecht (1990). 16 Makinde, O.D. and Mhone, P.Y. â€Å"Heat Transfer to MHD Oscillatory Flow in a Channel Filled with Porous Medium†. Rom. Journ. Phys. 50 (2005): 931-938. 17 Mehmood, A. and Ali, A. â€Å"The Effect of Slip Condition on Unsteady MHD Oscillatory Flow of a Viscous Fluid in a Planer Channel†. Rom. Journ. Phys. 52(1-2) (2007): 85-91. 18 Singh, K.D. and Garg, B.P. â€Å"Radiative Heat Transfer in MHD Oscillatory Flow through Porous Medium Bounded by Two Vertical Porous Plates†. Bull. Cal. Math. Soc.102(2) (2010) 129-138.

India Election

The current 1 5th Lok Sabha will complete its constitutional term on May 31 , 2014 By constitutional requirement, elections to the Lok Sabha must be held at most every five years or whenever parliament is dissolved by the president. The previous election, to the 1 5th Lok Sabha, was conducted in April-May 2009 and its term would naturally expire on 31 May 2014. The election will be organised by the Election Commission of India (EC') and are normally held in multiple phases to better handle the large electoral base and security concerns.Congress had a empathic victory in 2009 10k sabha elections . 1JPA- 2 started on a high by wining almost full majority of its own. However ,their second term has been marred with controversies and corruption allegations. starting with common wealth game scam,every few monthes saw a new scam coming out like Adarsh society scam and the biggest of all sharply in the past few years adding to the woes of common men. Cursed against black money and corruption by Ana Hazare and to some extent baba Ramdev has only added to the woes of congress. But congress is srewed and knows politics very well.They know that offence is the best way of defend. For every scam or corruption news come out ,they bounce back equally controversial news against Vival arties. Their projection of Rahul Gandhi,who is known as youth icon of India today after his appointment as vice-president of congress party. Lets see as a prime ministreal candidate may help them in their campaign build upto 2014 elections. Since the last general election, the BJP has made inroads by winning the state assembly elections in Goa and winning despite a tradition of anti-incumbency in Punjab.However, it lost control of Uttaranchal, Himachel Pradesh and its southern bastion of Karnataka. Use of technology In January 2013, the Election Commission of India announced that it would be using n SMS based alert system called Communication Plan for Election (COMET) during the election. The syst em, aimed at sending messages to the millions of government officials on election duty, was successfully deployed in the assembly polls in Goa, Punjab, Uttar Pradesh, Uttarakhand andManipur in early 2012 and in Himachal Pradesh and Gujarat in late 2012.The COMET system â€Å"uses coded text messages through mobile phones to collect data about officials, information about scheduled events like staff reaching the polling station, mock polls conducted, start of polling, oting percentages every two hours, number of voters in after voting time was over, and whether the poll party reached safely at the high security Electronic Voting Machine (EVMs) deposit centre. † The system would also send alerts to the local police in case of disturbances at any polling station Main opposition party Bhartiya Janta Party was left down and out after 2009 elections.BJPs arch enemy is not congres but BJP itself. lts leaders have failed to capitalize on core issues of price raise and corruption agai nst the congress. They shoud have learned from congress and other nd some other smaller parties,have been able to successfully use the anti miniorty tag againt the BJPfor ever two decades now. BJP has also lost a lot of mass appeal leaders over the years past popular leadrer in India Atal Behari Vajpayee has now retired from active politic. charsmatics learder and face of modern India ,Parmod MaJhan was killed in a tragic incident.Stalwarts like Govindacharya and Jaswant Singh were thrown out. Prime ministreal candidate Murli Manohar Joshi has been made to sit on the side lines with no influence on national level politics. L. K. Advani is lose to retirement years and fire brand Sushma SwaraJ hasn't proved to be a winner yet. That leaves the party with only one leadear of mass appeal,Narender Modi who may not yet able to handle national politics alone,and behind him a dark shade of communlist tag. Beside every one knows congress will play the anti miniorty tag against him quite well. BJP has also destoried its chance by not farming stretigc alliance with other parties in state. It used to have an alliance with AIADMK in Tamil Nadu and Mamta Banerjee'sTMS , IN West Bengal ,BJD in Orissa and recently JDU OF Bihar . BJPS loss has been congress gain. Third Fornt Parties: Third fornt parties have been redused to play a miniorty role at the center over the past few years. Leaders like Lalu Parsad,Mulayam Singh YadavJaya Lalta,Mayawati are no Govt. ln this case of congress.Left fornt has already become non-existent after the debaile in 2011 assembly elections and it had be highly unlikely that they,had make any come back by 2014. For the past few years, most of third fornt allies have been thob-nobbing with congress ,which raises doubt on their very existence. Third fornt was formed to combat BJP as well as congress ,but if u are going to chossse congress fter polls every time ,then won't it better for peoples to vote for congress dereibly third fornt needs to get its priorities right and decide on their future survavial options ,because as of now their future looks black.The contender's For India Election 2014 Though congress may not admit it yet,but Manmohan Singh be showen door out,and congress may be prefer to field Rahul Gandhi as its Prime Ministreal candidate in 2014. 1t may be too early for Rahul to lead nation as he has not proven his political accumen yet,but after the negative reviews UPA-2 is gathering,congress may want to hange Manmohan Singh. As for BJP the choice is only Narender Modi havng good record at regional level but no influence at national level yet. The Prime Ministreal Candidate: 1 Gandhi or Manmohan Singh. :NDA:- Narender Mod'. 3:Third Fornt:-Depends upon which party gets most seats. Slogans Of Parties: UPA:-Secularism NDA:-Hindu Rashtar OTHERS:-Rural Deviopment MANIFESTO:- UPA:-The congress president Mrs Sonia Gandhi and prime Minister Dr. Manmohan Singh realeasd the party manifesto,the menifestolists some promises wit h special focus on miniortes,dalits and tribal communities. Reiteraing its national rural employment gaurntee act schamethe congress has promised 100 days work for Rs 100a day,as an entitlement under MNAREGA.The congres has promised to enact a right to food law that gurantee food for all. lt has announced that every family living below poverty line will be entaitled 25 kg of rice or wheat per month at rate of3 3 per kg. The manifesto subsieded community kitchens,which will be set up in all cities for homeless peoples and migrants,with the support of the central govt. In the health sector,congress has declared that every family living below poverty line will be overed by the rashtrya swasthy bima youJna over the next three years. he party has promised social security cover for the disabaled,the elderly,urban home less,released bonded labourers,members of primitive tribalgroups and membersof the most backward dalit communites. S In order to woo the miniorites community,the congress pl ans to implement reservation for miniortes,on the basis of social and economic backwardness govt Jobs and educational institutions. The party has promised to set up an equal opportunity commission to ensure that the sachar commission recommendations are implemented and the miniortes are not deprived in any atter.The party has reterated the contenation promise of implementing33 % reservation for womens in parliament and he state legislature ,which it had to failed promised to reserve one third of all central govtJobs for womens. The congress has promised free education from primary till the university education for students from dali and tribalcommnites. continuing its incentives for the schedule castesand schedule tribe communites. To cheak communal and caste related violence,congress has proposed a law that empower the nationalhuman rights commission to monitor nvestigation and trail in all such cases.Declering a zero tolarence policy towards terrorism. The party has focused on its core areas of farmers ,womens,the socially backword sections. Through its wide range of promises,the congress is trying to projecta govt which will work on inclusive growth,encompassing all sections of society. NDA: 1,To develop a prosperous powerful Nation. 2,for stability and secular india needs a decive leader. 3,National security fear shall no longer stalk this land. 3,Engaging the world India' voice shall be heared.

Supernatural Elements in Jane Eyre - Free Essay Example

Sample details Pages: 3 Words: 796 Downloads: 3 Date added: 2019/05/08 Category Literature Essay Level High school Tags: Jane Eyre Essay Did you like this example? Throughout the novel Jane Eyre, Charlotte Bront incorporates Gothic elements†¢specifically the supernatural†¢to emphasize the eerie presence that follows, and essentially haunts, Jane through each of her endeavors. Although the reader perceives certain situations as supernatural, they are not truly supernatural in the novel. By creating such an atmosphere, Bront is able to utilize supernatural elements to convey significant revelations within Jane that ultimately change the course of her story. The first of many supernatural occurrences†¢and a very important one at that†¢presents itself at Gateshead Hall, following the cruelty inflicted upon Jane by her aunt, Mrs. Reed. While locked inside of the red-room, Jane views her reflection, which consisted of a white face and arms specking the gloom, and glittering eyes of fear moving where all else was still (Bront 20). Jane describes her reflection as [having] the effect of a real spirit (Bront 20). By depicting her reflection as unearthly, Bront shows the reader a glimpse of Janes inner view of herself. In comparison to those she lives with, Jane knows she is different, that she is merely plain and small. However, the glittering eyes Jane describes also highlights her differences in regard to the Reed family (Bront 20). Janes eyes are a representation of her passion, which begins to surface as a result of the injustices she endures at Gateshead. Although her passion first manifests itself as fear, it is still viewed as uncanny. Ultimately, Bront incorporates this scene into the novel because it not only foreshadows Janes passionate nature, but also the many encounters with others in which Jane is viewed as an odd character as a result of her plain exterior in comparison to her vibrant interior. Don’t waste time! Our writers will create an original "Supernatural Elements in Jane Eyre" essay for you Create order Because supernatural elements propel the novel, Janes encounters with the supernatural do not cease when she leaves Gateshead, but continue also into her time at Thornfield. At Thornfield, Jane unexpectedly finds herself a genuine home, one that she never imagined she would have. Gateshead and Lowood restricted Janes independence greatly, yet at Thornfield, she was able to develop into her own person. In the process of becoming herself, she repressed many of her fears, which the reader becomes aware of through the existence of Bertha Mason. On the night prior to the marriage between Jane and Mr. Rochester, Jane is visited by a woman, tall and large, with thick and dark hair hanging long down her back in the middle of the night (Bront 330). Jane describes Bertha as a woman with a savage face and red eyes (Bront 331). Although Bertha is a woman with a mental illness, Bront illustrates her as a supernatural creature because she embodies Janes inner self that is composed of fear and dark ness. Evidently, Berthas existence carries the intention of destroying Janes happiness and home at Thornfield†¢which has been Janes greatest fear since Mr. Rochester proposed to her. After her encounter with Bertha, she confesses her confusion to Rochester, who identifies her visions as mental terrors (Bront 332). However, Jane reveals to the reader that she only conceded to his ideas because she desired to please him†¢once again, suppressing her feelings to please Rochester. Despite Janes initial shock on their wedding day, Berthas existence actually triggers significant growth within Jane, in which she comes to the realization that she can only rely on herself for happiness. At Moor House, Jane unites with the family she did not know she had, which brings her content following Rochesters betrayal. Her journey to Moor House and the union with her family allows Jane to grow immensely within herself. However, Janes newfound strength is tested to its limits when St. John attempts to manipulate Jane into becoming his wife. In their final discussion, she agrees to marry him, only to be interrupted by the voice of Mr. Rochester. Evidently, Jane is perplexed by these sounds, as they were [spoken] in pain and woe†¢wildly, eerily, urgently (Bront 485). Immediately, Jane realizes that she must pursue him or she will live with regret. This instance alone signifies Janes strength because she was able to deny St. John and instead seek what her heart desired. When Jane and Rochester eventually reunite, the reader learns that Rochester did call for Jane on the same night she heard his voice. Bront incorporates this otherworldly connection between them to signify th at they are two souls meant for one another. The decision to leave Moor House to marry Rochester demonstrates the overall growth of Jane throughout the novel, who developed into an individual capable of deciding her own fate. Essentially, Bront incorporates the supernatural to create an atmosphere of suspense, yet also achieves a deeper meaning by doing so. When Jane encountered the supernatural, she often grew from the experience and triggered a change in her demeanor despite her initial fears.