Publications

2002
Kubicki M, Westin C-F, Maier SE, Mamata H, Frumin M, Ersner-Hershfield H, Kikinis R, Jolesz FA, McCarley R, Shenton ME. Diffusion tensor imaging and its application to neuropsychiatric disorders. Harv Rev Psychiatry. 2002;10 (6) :324-36.Abstract
Magnetic resonance diffusion tensor imaging (DTI) is a new technique that can be used to visualize and measure the diffusion of water in brain tissue; it is particularly useful for evaluating white matter abnormalities. In this paper, we review research studies that have applied DTI for the purpose of understanding neuropsychiatric disorders. We begin with a discussion of the principles involved in DTI, followed by a historical overview of magnetic resonance diffusion-weighted imaging and DTI and a brief description of several different methods of image acquisition and quantitative analysis. We then review the application of this technique to clinical populations. We include all studies published in English from January 1996 through March 2002 on this topic, located by searching PubMed and Medline on the key words "diffusion tensor imaging" and "MRI." Finally, we consider potential future uses of DTI, including fiber tracking and surgical planning and follow-up.
Lee CU, Shenton ME, Salisbury DF, Kasai K, Onitsuka T, Dickey CC, Yurgelun-Todd D, Kikinis R, Jolesz FA, McCarley RW. Fusiform gyrus volume reduction in first-episode schizophrenia: a magnetic resonance imaging study. Arch Gen Psychiatry. 2002;59 (9) :775-81.Abstract
BACKGROUND: The fusiform gyrus (occipitotemporal gyrus) is thought to be critical for face recognition and may possibly be associated with impaired facial recognition and interpretation of facial expression in schizophrenia. of postmortem studies have suggested that fusiform gyrus volume is reduced in schizophrenia, but there have been no in vivo structural studies of the fusiform gyrus in schizophrenia using magnetic resonance imaging. METHODS: High-spatial resolution magnetic resonance images were used to measure the gray matter volume of the fusiform gyrus in 22 patients with first-episode schizophrenia (first hospitalization), 20 with first-episode affective psychosis (mainly manic), and 24 control subjects. RESULTS: Patients with first-episode schizophrenia had overall smaller relative volumes (absolute volume/intracranial contents) of fusiform gyrus gray matter compared with controls (9%) and patients with affective psychosis (7%). For the left fusiform gyrus, patients with schizophrenia showed an 11% reduction compared with controls and patients with affective psychosis. Right fusiform gyrus volume differed in patients with schizophrenia only compared with controls (8%). CONCLUSION: Schizophrenia is associated with a bilateral reduction in fusiform gyrus gray matter volume that is evident at the time of first hospitalization and is different from the presentation of affective psychosis.
Levitt JJ, McCarley RW, Dickey CC, Voglmaier MM, Niznikiewicz MA, Seidman LJ, Hirayasu Y, Ciszewski AA, Kikinis R, Jolesz FA, et al. MRI study of caudate nucleus volume and its cognitive correlates in neuroleptic-naive patients with schizotypal personality disorder. Am J Psychiatry. 2002;159 (7) :1190-7.Abstract
OBJECTIVE: "Cognitive" circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. METHOD: Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. RESULTS: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. CONCLUSIONS: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum.
Hirose M, Bharatha A, Hata N, Zou KH, Warfield SK, Cormack RA, D'Amico A, Kikinis R, Jolesz FA, Tempany CM. Quantitative MR Imaging Assessment of Prostate Gland Deformation before and during MR Imaging-guided Brachytherapy. Acad Radiol. 2002;9 (8) :906-12.Abstract

RATIONALE AND OBJECTIVES: The authors performed this study to document the deformations that occur between pretreatment magnetic resonance (MR) imaging and intraoperative MR imaging during brachytherapy. MATERIALS AND METHODS: MR images obtained at 1.5 and 0.5 T in 10 patients with prostate cancer were analyzed for changes in the shape and substructure of the prostate. Three-dimensional models of the prostate were obtained. The authors measured anteroposterior dimension; total gland, peripheral zone, and central gland volumes; transverse dimension; and superoinferior height. RESULTS: Gland deformations were seen at visual inspection of the three-dimensional models. The anteroposterior dimension of the total gland, central gland, and peripheral zone increased from 1.5- to 0.5-T imaging (median dimension, 4.9, 1.5, and 1.8 mm, respectively), and the increase was greatest in the peripheral zone (P < .05, all comparisons). There was a decrease in the transverse dimension from 1.5- to 0.5-T imaging (median, 4.5 mm; P < .005). The total gland volume and the superoinferior height did not show a statistically significant change. CONCLUSION: There were significant deformations in the shape of the prostate, especially in the peripheral zone, between the two imaging studies. The likely causes of the shape change are differences in rectal filling (endorectal coil used in 1.5-T studies vs obturator in 0.5-T studies) and/or changes in patient position (supine vs lithotomy). These findings suggest that pretreatment images alone may not be reliable for accurate therapy planning. It may be useful to integrate pre-and intraoperative data.

Ferrant M, Nabavi A, Macq B, Black PM, Jolesz FA, Kikinis R, Warfield SK. Serial registration of intraoperative MR images of the brain. Med Image Anal. 2002;6 (4) :337-59.Abstract
The increased use of image-guided surgery systems during neurosurgery has brought to prominence the inaccuracies of conventional intraoperative navigation systems caused by shape changes such as those due to brain shift. We propose a method to track the deformation of the brain and update preoperative images using intraoperative MR images acquired at different crucial time points during surgery. We use a deformable surface matching algorithm to capture the deformation of boundaries of key structures (cortical surface, ventricles and tumor) throughout the neurosurgical procedure, and a linear finite element elastic model to infer a volumetric deformation. The boundary data are extracted from intraoperative MR images using a real-time intraoperative segmentation algorithm. The algorithm has been applied to a sequence of intraoperative MR images of the brain exhibiting brain shift and tumor resection. Our results characterize the brain shift after opening of the dura and at the different stages of tumor resection, and brain swelling afterwards. Analysis of the average deformation capture was assessed by comparing landmarks identified manually and the results indicate an accuracy of 0.7+/-0.6 mm (mean+/-S.D.) for boundary surface landmarks, of 0.9+/-0.6 mm for landmarks inside the boundary surfaces, and 1.6+/-0.9 mm for landmarks in the vicinity of the tumor.
Kubicki M, Shenton ME, Salisbury DF, Hirayasu Y, Kasai K, Kikinis R, Jolesz FA, McCarley RW. Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage. 2002;17 (4) :1711-9.Abstract

Voxel-based morphometry (VBM) may afford a more rapid and extensive survey of gray matter abnormalities in schizophrenia than manually drawn region of interest (ROI) analysis, the current gold standard in structural MRI. Unfortunately, VBM has not been validated by comparison with ROI analyses, nor used in first-episode patients with schizophrenia or affective psychosis, who lack structural changes associated with chronicity. An SPM99-based implementation of VBM was used to compare a group of 16 patients with first-episode schizophrenia and a group of 18 normal controls and, as a further comparison, 16 first-episode patients with affective psychosis. All groups were matched for age and handedness. High spatial resolution structural images were normalized to the SPM99 template and then segmented, smoothed, and subjected to an ANCOVA. Schizophrenia vs control group comparisons: Voxel-by-voxel comparison of gray matter densities showed that only the left STG region was significantly different when corrected for multiple comparisons (P <.05), consistent with our previously reported manual ROI results. Analysis of the extent of voxel clusters, replicated with permutation analyses, revealed group differences in bilateral anterior cingulate gyri and insula (not previously examined by us with manually drawn ROI) and unilateral parietal lobe, but not in medial temporal lobe (where our ROI analysis had shown differences). However, use of a smaller smoothing kernel and a small volume correction revealed left-sided hippocampal group differences. Affective psychosis comparisons: When the same statistical thresholding criteria were used, no significant differences between affective psychosis patients and controls were noted. Since a major interest was whether patients with affective psychosis shared some anatomical abnormalities with schizophrenia, we applied a small volume correction and searched within the regions that were significantly less dense in schizophrenia compared to control subjects. With this statistical correction, the insula showed, bilaterally, the same pattern of differences in affective disorder subjects as that in schizophrenic subjects, whereas both left STG and left hippocampus showed statistical differences between affectives and schizophrenics, indicating the abnormalities specific to first-episode schizophrenia. These findings suggest both the promise and utility of VBM in evaluating gray matter abnormalities. They further suggest the importance of comparing VBM findings with more traditional ROI analyses until the reasons for the differences between methods are determined.

2001
Kaus MR, Warfield SK, Nabavi A, Black PM, Jolesz FA, Kikinis R. Automated Segmentation of MR Images of Brain Tumors. Radiology. 2001;218 (2) :586-91.Abstract

An automated brain tumor segmentation method was developed and validated against manual segmentation with three-dimensional magnetic resonance images in 20 patients with meningiomas and low-grade gliomas. The automated method (operator time, 5-10 minutes) allowed rapid identification of brain and tumor tissue with an accuracy and reproducibility comparable to those of manual segmentation (operator time, 3-5 hours), making automated segmentation practical for low-grade gliomas and meningiomas.

Jolesz FA, Nabavi A, Kikinis R. Integration of Interventional MRI with Computer-assisted Surgery. J Magn Reson Imaging. 2001;13 (1) :69-77.Abstract

Interventional MRI (IMRI) has entered into a new stage in which computer-based techniques play an increasing role in planning, monitoring, and controlling the procedures. The use of interactive imaging, navigational image guidance techniques, and image processing methods is demonstrated in various applications. The integration of intraoperative MRI guidance and computer-assisted surgery will greatly accelerate the clinical utility of image-guided therapy in general and interventional MRI in particular. J. Magn. Reson. Imaging 2001;13:69-77.

Mamata Y, Mamata H, Nabavi A, Kacher DF, Pergolizzi RS, Schwartz RB, Kikinis R, Jolesz FA, Maier SE. Intraoperative diffusion imaging on a 0.5 Tesla interventional scanner. J Magn Reson Imaging. 2001;13 (1) :115-9.Abstract
Intraoperative line scan diffusion imaging (LSDI) on a 0.5 Tesla interventional MRI was performed during neurosurgery in three patients. Diffusion trace images were obtained in acute ischemic cases. Scan time per slice was 46 seconds and 94 seconds, respectively, for diffusion tensor images. Diagnosis of acutely developed vascular occlusion was confirmed with follow-up scans. White matter tracts were displayed with the principal eigenvectors and provided guidance for the tumor surgery. In all cases, the diagnostic utility of LSDI was established. J. Magn. Reson. Imaging 2001;13:115-119.
Sperling RA, Guttmann CRG, Hohol MJ, Warfield SK, Jakab M, Parente M, Diamond EL, Daffner KR, Olek MJ, Orav EJ, et al. Regional Magnetic Resonance Imaging Lesion Burden and Cognitive Function in Multiple Sclerosis: A Longitudinal Study. Arch Neurol. 2001;58 (1) :115-21.Abstract

OBJECTIVE: To investigate the relationship between magnetic resonance imaging regional lesion burden and cognitive performance in multiple sclerosis (MS) over a 4-year follow-up period. DESIGN: Twenty-eight patients with MS underwent magnetic resonance imaging and took the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis at baseline, 1-year, and 4-year follow-up. An automated 3-dimensional lesion detection method was used to identify MS lesions within anatomical regions on proton density T2-weighted images. The relationship between magnetic resonance imaging regional lesion volumes and the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis results was examined using regression analyses. RESULTS: At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared with age- and educational level-matched control subjects, patients with MS showed significant impairment on tests of sustained attention, processing speed, and verbal memory (P<.001). Performance on these measures was negatively correlated with MS lesion volume in frontal and parietal regions at baseline, 1-year, and 4-year follow-up (R = -0.55 to -0.73, P<.001). CONCLUSIONS: Multiple sclerosis lesions show a propensity for frontal and parietal white matter. Lesion burden in these areas was strongly associated with performance on tasks requiring sustained complex attention and working verbal memory. This relationship was consistent over a 4-year period, suggesting that disruption of frontoparietal subcortical networks may underlie the pattern of neuropsychological impairment seen in many patients with MS.

Lorigo L, Faugeras OD, Grimson WE, Keriven R, Kikinis R, Nabavi A, Westin C-F. CURVES: Curve Evolution for Vessel Segmentation. Med Image Anal. 2001;5 (3) :195-206.Abstract

The vasculature is of utmost importance in neurosurgery. Direct visualization of images acquired with current imaging modalities, however, cannot provide a spatial representation of small vessels. These vessels, and their branches which show considerable variations, are most important in planning and performing neurosurgical procedures. In planning they provide information on where the lesion draws its blood supply and where it drains. During surgery the vessels serve as landmarks and guidelines to the lesion. The more minute the information is, the more precise the navigation and localization of computer guided procedures. Beyond neurosurgery and neurological study, vascular information is also crucial in cardiovascular surgery, diagnosis, and research. This paper addresses the problem of automatic segmentation of complicated curvilinear structures in three-dimensional imagery, with the primary application of segmenting vasculature in magnetic resonance angiography (MRA) images. The method presented is based on recent curve and surface evolution work in the computer vision community which models the object boundary as a manifold that evolves iteratively to minimize an energy criterion. This energy criterion is based both on intensity values in the image and on local smoothness properties of the object boundary, which is the vessel wall in this application. In particular, the method handles curves evolving in 3D, in contrast with previous work that has dealt with curves in 2D and surfaces in 3D. Results are presented on cerebral and aortic MRA data as well as lung computed tomography (CT) data.

Ruiz-Alzola J, Kikinis R, Westin C-F. Detection of Point Landmarks in Multidimensional Tensor Data. Signal Processing. 2001;81 (10) :2243-47.Abstract

This paper describes a unified approach to the detection of point landmarks-whose neighborhoods convey discriminant information-including multidimensional scalar, vector, and higher-order tensor data. The method is based on the interpretation of generalized correlation matrices derived from the gradient of tensor functions, a probabilistic interpretation of point landmarks, and the application of tensor algebra. Results on both synthetic and real tensor data are presented.

Kordelle J, Richolt JA, Millis M, Jolesz FA, Kikinis R. Development of the Acetabulum in Patients with Slipped Capital Femoral Epiphysis: A Three-dimensional Analysis Based on Computed Tomography. J Pediatr Orthop. 2001;21 (2) :174-8.Abstract

Orientation and shape of the acetabulum were determined by the use of three-dimensional reconstruction of computed tomography (CT) data sets in 22 patients with a total of 30 slipped capital femoral epiphyses. We developed an interactive three-dimensional software program to measure the anteversion and inclination of the acetabulum without projectional and pelvis-tilting errors. Furthermore, we determined the height, width, depth, volume, and surface of the acetabulum as parameters describing the acetabular shape. Comparison of the affected side with the contralateral unaffected hip showed no significant differences for acetabular orientation and shape. The relationship between the degree of the slip and the acetabular orientation was calculated. No correlation was found. Based on the results of this study, we conclude that the slipping of the capital femoral epiphysis has no influence on acetabular development.

Gering D, Nabavi A, Kikinis R, Hata N, O'Donnell LJ, Grimson EWL, Jolesz FA, Black PM, Wells III WM. An Integrated Visualization System for Surgical Planning and Guidance using Image Fusion and an Open MR. J Magn Reson Imaging. 2001;13 (6) :967-75.Abstract

A surgical guidance and visualization system is presented, which uniquely integrates capabilities for data analysis and on-line interventional guidance into the setting of interventional MRI. Various pre-operative scans (T1- and T2-weighted MRI, MR angiography, and functional MRI (fMRI)) are fused and automatically aligned with the operating field of the interventional MR system. Both pre-surgical and intra-operative data may be segmented to generate three-dimensional surface models of key anatomical and functional structures. Models are combined in a three-dimensional scene along with reformatted slices that are driven by a tracked surgical device. Thus, pre-operative data augments interventional imaging to expedite tissue characterization and precise localization and targeting. As the surgery progresses, and anatomical changes subsequently reduce the relevance of pre-operative data, interventional data is refreshed for software navigation in true real time. The system has been applied in 45 neurosurgical cases and found to have beneficial utility for planning and guidance. J. Magn. Reson. Imaging 2001;13:967-975.

Hata N, Jinzaki M, Kacher DF, Cormak R, Gering D, Nabavi A, G SS, D'Amico AV, Kikinis R, Jolesz FA, et al. MR Imaging-guided Prostate Biopsy with Surgical Navigation Software: Device Validation and Feasibility. Radiology. 2001;220 (1) :263-8.Abstract

Magnetic resonance (MR) imaging--guided prostate biopsy in a 0.5-T open imager is described, validated in phantom studies, and performed in two patients. The needles are guided by using fast gradient-recalled echo and T2-weighted fast spin-echo images. Surgical navigation software provided T2-weighted images critical to targeting the peripheral zone and the tumor. MR imaging can be used to guide prostate biopsy.

Hirayasu Y, Tanaka S, Shenton ME, Salisbury DF, Desantis MA, Levitt JJ, Wible CG, Yurgelun-Todd D, Kikinis R, Jolesz FA, et al. Prefrontal Gray Matter Volume Reduction in First Episode Schizophrenia. Cereb Cortex. 2001;11 (4) :374-81.Abstract
Functional measures have consistently shown prefrontal abnormalities in schizophrenia. However, structural magnetic resonance imaging (MRI) findings of prefrontal volume reduction have been less consistent. In this study, we evaluated prefrontal gray matter volume in first episode (first hospitalized) patients diagnosed with schizophrenia, compared with first episode patients diagnosed with affective psychosis and normal comparison subjects, to determine the presence in and specificity of prefrontal abnormalities to schizophrenia. Prefrontal gray and white matter volumes were measured from first episode patients with schizophrenia (n = 17), and from gender and parental socio-economic status-matched subjects with affective (mainly manic) psychosis (n = 17) and normal comparison subjects (n = 17), age-matched within a narrow age range (18--29 years). Total (left and right) prefrontal gray matter volume was significantly reduced in first episode schizophrenia compared with first episode affective psychosis and comparison subjects. Follow-up analyses indicated significant left prefrontal gray matter volume reduction and trend level reduction on the right. Schizophrenia patients showed 9.2% reduction on the left and 7.7% reduction on the right compared with comparison subjects. White matter volumes did not differ among groups. These data suggest that prefrontal cortical gray matter volume reduction is selectively present at first hospitalization in schizophrenia but not affective psychosis.
Nabavi A, Black PM, Gering D, Westin C-F, Mehta V, Pergolizzi R, Ferrant M, Warfield SK, Hata N, Schwartz R, et al. Serial Intraoperative Magnetic Resonance Imaging of Brain Shift. Neurosurgery. 2001;48 (4) :787-97; discussion 797-8.Abstract

OBJECTIVE: A major shortcoming of image-guided navigational systems is the use of preoperatively acquired image data, which does not account for intraoperative changes in brain morphology. The occurrence of these surgically induced volumetric deformations ("brain shift") has been well established. Maximal measurements for surface and midline shifts have been reported. There has been no detailed analysis, however, of the changes that occur during surgery. The use of intraoperative magnetic resonance imaging provides a unique opportunity to obtain serial image data and characterize the time course of brain deformations during surgery. METHODS: The vertically open intraoperative magnetic resonance imaging system (SignaSP, 0.5 T; GE Medical Systems, Milwaukee, WI) permits access to the surgical field and allows multiple intraoperative image updates without the need to move the patient. We developed volumetric display software (the 3D Slicer) that allows quantitative analysis of the degree and direction of brain shift. For 25 patients, four or more intraoperative volumetric image acquisitions were extensively evaluated. RESULTS: Serial acquisitions allow comprehensive sequential descriptions of the direction and magnitude of intraoperative deformations. Brain shift occurs at various surgical stages and in different regions. Surface shift occurs throughout surgery and is mainly attributable to gravity. Subsurface shift occurs during resection and involves collapse of the resection cavity and intraparenchymal changes that are difficult to model. CONCLUSION: Brain shift is a continuous dynamic process that evolves differently in distinct brain regions. Therefore, only serial imaging or continuous data acquisition can provide consistently accurate image guidance. Furthermore, only serial intraoperative magnetic resonance imaging provides an accurate basis for the computational analysis of brain deformations, which might lead to an understanding and eventual simulation of brain shift for intraoperative guidance.

Westin C-F, Wigström L, Loock T, Sjöqvist L, Kikinis R, Knutsson H. Three-dimensional Adaptive Filtering in Magnetic Resonance Angiography. J Magn Reson Imaging. 2001;14 (1) :63-71.Abstract

In order to enhance 3D image data from magnetic resonance angiography (MRA), a novel method based on the theory of multidimensional adaptive filtering has been developed. The purpose of the technique is to suppress image noise while enhancing important structures. The method is based on local structure estimation using six 3D orientation selective filters, followed by an adaptive filtering step controlled by the local structure information. The complete filtering procedure requires approximately 3 minutes of computational time on a standard workstation for a 256 x 256 x 64 data set. The method has been evaluated using a mathematical vessel model and in vivo MRA data (both phase contrast and time of flight (TOF)). 3D adaptive filtering results in a better delineation of small blood vessels and efficiently reduces the high-frequency noise. Depending on the data acquisition and the original data type, contrast-to-noise ratio (CNR) improvements of up to 179% (8.9 dB) were observed. 3D adaptive filtering may provide an alternative to prolonging the scan time or using contrast agents in MRA when the CNR is low.

Kordelle J, Millis M, Jolesz FA, Kikinis R, Richolt JA. Three-dimensional Analysis of the Proximal Femur in Patients with Slipped Capital Femoral Epiphysis Based on Computed Tomography. J Pediatr Orthop. 2001;21 (2) :179-82.Abstract

A three-dimensional (3D) analysis based on computed tomography was performed to study the 3D geometry of the proximal femur in cases of slipped capital femoral epiphysis (SCFE). For this purpose, new interactive software was developed to analyze hip joint geometry using 3D models without pelvis tilting and projected errors. Twenty-two patients, 8 girls and 14 boys, with a total of 30 slipped capital femoral epiphyses, were reviewed. In the affected hips, we observed a reduced femoral anteversion of 7.0 degrees (vs. 12.7 degrees) and a reduced femoral shaft neck angle of 134.2 degrees (vs. 141.0 degrees). In response to these results, we suggest that an SCFE is associated with reduced femoral anteversion and a reduced femoral shaft neck angle.

Gugino LD, Romero JR, Aglio LS, Titone D, Ramirez M, Pascual-Leone A, Grimson EWL, Weisenfeld N, Kikinis R, Shenton ME. Transcranial Magnetic Stimulation Coregistered with MRI: A Comparison of a Guided versus Blind Stimulation Technique and its Effect on Evoked Compound Muscle Action Potentials. Clin Neurophysiol. 2001;112 (10) :1781-92.Abstract
INTRODUCTION AND METHODS: Compound muscle action potentials (CMAPs) elicited by transcranial magnetic stimulation (TMS) are characterized by enormous variability, even when attempts are made to stimulate the same scalp location. This report describes the results of a comparison of the spatial errors in coil placement and resulting CMAP characteristics using a guided and blind TMS stimulation technique. The former uses a coregistration system, which displays the intersection of the peak TMS induced electric field with the cortical surface. The latter consists of the conventional placement of the TMS coil on the optimal scalp position for activation of the first dorsal interossei (FDI) muscle. RESULTS: Guided stimulation resulted in significantly improved spatial precision for exciting the corticospinal projection to the FDI compared to blind stimulation. This improved precision of coil placement was associated with a significantly increased probability of eliciting FDI responses. Although these responses tended to have larger amplitudes and areas, the coefficient of variation between guided and blind stimulation induced CMAPs did not significantly differ. CONCLUSION: The results of this study demonstrate that guided stimulation improves the ability to precisely revisit previously stimulated cortical loci as well as increasing the probability of eliciting TMS induced CMAPs. Response variability, however, is due to factors other than coil placement.

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