Thesis (M.D.)—Boston University

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Thesis (Ph.D)--Electrical and Computer Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Oskar krinjar; Committee Member: Allen Tannenbaum; Committee Member: Anthony Yezzi; Committee Member: John Oshinski; Committee Member: Patricio Vela. Part of the SMARTech Electronic Thesis and Dissertation Collection.

In this dissertation, the accuracy and reliability of non-linear finite element computations in application to surgical simulation is evaluated. The evaluation is performed through comparison between the experiment and finite element analysis of indentation of soft tissue phantom and human brain phantom. The evaluation is done in terms of the forces acting on the cylindrical Aluminium indenter and deformation of the phantoms due to these forces. The deformation of the phantoms is measured by tracking 3D motions of X-ray opaque markers implanted in the direct neighbourhood under the indenter using a custom-made biplane X-ray image intensifiers (XRII) system. The phantoms are made of Sylgard® 527 gel to simulate the hyperelastic constitutive behaviour of the brain tissue. The phantoms are prepared layer by layer to facilitate the implantation of the X-ray opaque markers. The modelling of soft tissue phantom indentation and human brain phantom indentation is performed using the ABAQUSTM/Standard finite element solver. Realistic geometry model of the human brain phantom obtained from Magnetic Resonance images is used. Specific constitutive properties of the phantom layers determined through uniaxial compression tests are used in the model. The models accurately predict the indentation force-displacement relations and marker displacements in both soft tissue phantom indentation and human brain phantom indentation. Good agreement between the experimental and modelling results verifies the reliability and accuracy of the finite element analysis techniques used in this study and confirms the predictive power of these techniques in application to surgical simulation.

For children with intractable seizures, surgical removal of epileptic foci, if identifiable and feasible, can be an effective way to reduce or eliminate seizures. The success of this type of surgery strongly hinges upon the ability to identify and demarcate those epileptic foci. The ultimate goal of this research project is to develop an effective technology for detection of unique in vivo pathophysiological characteristics of epileptic cortex and, subsequently, to use this technology to guide epilepsy surgery intraoperatively. In this PhD dissertation the feasibility of using optical spectroscopy to identify unique in vivo pathophysiological characteristics of epileptic cortex was evaluated and proven using the data collected from children undergoing epilepsy surgery. In this first in vivo human study, static diffuse reflectance and fluorescence spectra were measured from the epileptic cortex, defined by intraoperative ECoG, and its surrounding tissue from pediatric patients undergoing epilepsy surgery. When feasible, biopsy samples were taken from the investigated sites for the subsequent histological analysis. Using the histological data as the gold standard, spectral data was analyzed with statistical tools. The results of the analysis show that static diffuse reflectance spectroscopy and its combination with static fluorescence spectroscopy can be used to effectively differentiate between epileptic cortex with histopathological abnormalities and normal cortex in vivo with a high degree of accuracy. To maximize the efficiency of optical spectroscopy in detecting and localizing epileptic cortex intraoperatively, the static system was upgraded to investigate histopathological abnormalities deep within the epileptic cortex, as well as to detect unique temporal pathophysiological characteristics of epileptic cortex. Detection of deep abnormalities within the epileptic cortex prompted a redesign of the fiberoptic probe. A mechanical probe holder was also designed and constructed to maintain the probe contact pressure and contact point during the time dependent measurements. The dynamic diffuse reflectance spectroscopy system was used to characterize in vivo pediatric epileptic cortex. The results of the study show that some unique wavelength dependent temporal characteristics (e.g., multiple horizontal bands in the correlation coefficient map g(λref = 800 nm, λcomp,t)) can be found in the time dependent recordings of diffuse reflectance spectra from epileptic cortex defined by ECoG.

Deep brain stimulation (DBS) surgery, a type of microelectrode-guided surgery, is an effective treatment for the movement disorders patients that can no longer be treated by medications. New rigid and non-rigid image registration methods were developed for the movement disorders patients that underwent DBS surgery. These new methods help study and analyze the brain shift during the DBS surgery and perform atlas-based segmentation of the deep brain structures for the DBS surgery planning and navigation. A diploë based rigid registration method for the intra-operative brain shift analysis during the DBS surgery was developed. The proposed method for the brain shift analysis ensures rigid registration based on diploë only, which can be treated as a rigid structure as opposed to the brain tissues. The results show that the brain shift during the DBS surgery is comparable to the size of the DBS targets and should not be neglected. This brain shift may further lengthen and complicate the DBS surgery contrary to the common belief that brain shift during the DBS surgery is not considerable. We also developed an integrated electrophysiological and anatomical atlas with eleven deep brain structures segmented by an expert, and electrophysiological data of four implant locations obtained from post-op MRI data of twenty patients that underwent DBS surgery. This atlas MR image is then non-rigidly registered with the pre-operative patient MR image, which provides initial DBS target location along with the segmented deep brain structures that can be used for guidance during the microelectrode mapping of the stereotactic procedure. The atlas based approach predicts the target automatically as opposed to the manual selection currently used. The results showed that 85% of the times, this automatic selection of the target location was closer to the target when compared to currently used technique.

Repetitiv navigerad transkraniell magnetstimulering (rnTMS) används preoperativt för att kartlägga kortikala, språkligt relevanta områden i hjärnan. I nuläget används substantivbenämning vid rnTMS, men det råder delade uppfattningar i aktuell forskning huruvida substantiv- eller verbbenämning är känsligast för stimulering och därför krävs mer forskning inom området. I föreliggande studie kompletterades substantivbenämningen med verbbenämning. Alla deltagare genomgick även preoperativ språklig testning och en av deltagarna genomgick också postoperativ språklig testning. Syftet med föreliggande studie var att jämföra skillnader vid expressiv språklig förmåga vid substantiv- och verbbenämning och att kartlägga språkliga funktioners utbredning i hjärnan, samt att identifiera ytterligare kliniska markörer för bestående språkliga svårigheter efter hjärnkirurgi. Studien syftade även till att undersöka huruvida det preoperativa rnTMS-resultatet överensstämmer med det postoperativa kirurgiresultatet. Studien hade fem deltagare, varav tre med hjärntumör och två med epilepsi, som skulle genomgå vaken hjärnkirurgi. Deltagarnas rnTMS- undersökning videoinspelades och deras språkliga testning ljudinspelades. Analyser genomfördes på individ- och gruppnivå. Resultaten visade att stimulering under verbbenämning inte orsakade signifikant fler felsvar än stimulering vid substantivbenämning, även om felsvaren vid verbbenämning var procentuellt fler. Däremot resulterade de två ordklasserna i olika felsvarslokalisationer hos samtliga deltagare. De tre vanligaste typerna av felsvar på gruppnivå var ändring av grammatisk ändelse, tvekljud samt byte till synonym och de vanligaste felsvarslokalisationena var gyrus frontalis medius, gyrus frontalis inferior och gyrus precentralis. Gällande den språkliga testningen fick deltagarna väldigt spridda resultat. Sammanfattningsvis verkar benämning av substantiv och verb komplettera varandra och båda ordklasserna bör användas vid rnTMS om metoden fortsätter att användas. Även patienternas högre språkliga förmåga (HLL) bör testas inför hjärnkirurgi. Avslutningsvis indikerar resultaten på att språkets placering i hjärnan är både mycket utbredd och väldigt individuell. / Repetitive navigated transcranial magnetic stimulation (rnTMS) is used preoperatively to map cortical areas in the brain that are important for language. Object naming is currently being used during rnTMS, but current research has differing opinions on whether naming of objects or actions are most sensitive to stimulation. Therefore, further research is needed in the field. In this study, object naming was combined with action naming. All of the participants also underwent language tests preoperatively and one of the participants underwent postoperative language tests as well. The aim of the present study was to compare differences in expressive language during object and action naming as well as to map the distribution of language functions in the brain. A further aim was to identify clinical markers of language difficulties following brain surgery and to investigate whether the preoperative rnTMS result corresponds with the postoperative brain surgery result. The present study had five participants, three with a brain tumor and two with epilepsy, who would undergo awake brain surgery. The rnTMS examination was video recorded and the language tests were audio recorded. All the examinations were analyzed at individual and group level. The results showed that stimulation during action naming did not cause significantly more errors than during object naming, although the errors for action naming were percentually higher. Errors during action naming and object naming for all participants had different localisations. The most common type of errors were change of grammatical ending, hesitations and change to synonym. The most common localisations of errors were gyrus frontalis medius, gyrus frontalis inferior and gyrus precentralis. The results of the language tests demonstrated a large variation. In conclusion, object and action naming seems to complement each other and should be used together during rnTMS if the method continues to be used. It is also important that High-Level Language (HLL) is tested before brain surgery. Lastly, the results indicate that the placements of language functions in the brain are both very widespread and very individual.