Comparison of seeding methods for visualization of the corticospinal tracts using single tensor tractography.

OBJECTIVES: To compare five different seeding methods to delineate hand, foot, and lip components of the corticospinal tract (CST) using single tensor tractography. METHODS: We studied five healthy subjects and 10 brain tumor patients. For each subject, we used five different seeding methods, from (1) cerebral peduncle (CP), (2) posterior limb of the internal capsule (PLIC), (3) white matter subjacent to functional MRI activations (fMRI), (4) whole brain and then selecting the fibers that pass through both fMRI and CP (WBF-CP), and (5) whole brain and then selecting the fibers that pass through both fMRI and PLIC (WBF-PLIC). Two blinded neuroradiologists rated delineations as anatomically successful or unsuccessful tractography. The proportions of successful trials from different methods were compared by Fisher's exact test. RESULTS: To delineate hand motor tract, seeding through fMRI activation areas was more effective than through CP (p<0.01), but not significantly different from PLIC (p>0.1). WBF-CP delineated hand motor tracts in a larger proportion of trials than CP alone (p<0.05). Similarly, WBF-PLIC depicted hand motor tracts in a larger proportion of trials than PLIC alone (p<0.01). Foot motor tracts were delineated in all trials by either PLIC or whole brain seeding (WBF-CP and WBF-PLIC). Seeding from CP or fMRI activation resulted in foot motor tract visualization in 87% of the trials (95% confidence interval: 60-98%). The lip motor tracts were delineated only by WBF-PLIC and in 36% of trials (95% confidence interval: 11-69%). CONCLUSIONS: Whole brain seeding and then selecting the tracts that pass through two anatomically relevant ROIs can delineate more plausible hand and lip motor tracts than seeding from a single ROI. Foot motor tracts can be successfully delineated regardless of the seeding method used.

Perfusion Imaging of Focal Cortical Dysplasia Using Arterial Spin Labeling: Correlation With Histopathological Vascular Density.

Focal cortical dysplasia is the most common malformation of cortical development, causing intractable epilepsy. This study investigated the relationship between brain perfusion and microvessel density in 7 children with focal cortical dysplasia. The authors analyzed brain perfusion measurements obtained by magnetic resonance imaging of 2 of the children and the microvessel density of brain tissue specimens obtained by epilepsy surgery on all of the children. Brain perfusion was approximately 2 times higher in the area of focal cortical dysplasia compared to the contralateral side. The microvessel density was nearly double in the area of focal cortical dysplasia compared to the surrounding cortex that did not have morphological abnormalities. These findings suggest that hyperperfusion can be related to increased microvessel density in focal cortical dysplasia rather than only to seizures. Further investigations are needed to determine the relationship between brain perfusion, microvessel density, and seizure activity.

The fiber laterality histogram: a new way to measure white matter asymmetry.

The quantification of brain asymmetries may provide biomarkers for presurgical localization of language function and can improve our understanding of neural structure-function relationships in health and disease. We propose a new method for studying the asymmetry of the white matter tracts in the entire brain, and we apply it to a preliminary study of normal subjects across the handedness spectrum. Methods for quantifying white matter asymmetry using diffusion MRI tractography have thus far been based on comparing numbers of fibers or volumes of a single fiber tract across hemispheres. We propose a generalization of such methods, where the "number of fibers" laterality measurement is extended to the entire brain using a soft fiber comparison metric. We summarize the distribution of fiber laterality indices over the whole brain in a histogram, and we measure properties of the distribution such as its skewness, median, and inter-quartile range. The whole-brain fiber laterality histogram can be measured in an exploratory fashion without hypothesizing asymmetries only in particular structures. We demonstrate an overall difference in white matter asymmetry in consistent- and inconsistent-handers: the skewness of the fiber laterality histogram is significantly different across handedness groups.

A combined fMRI and DTI examination of functional language lateralization and arcuate fasciculus structure: Effects of degree versus direction of hand preference.

The present study examined the relationship between hand preference degree and direction, functional language lateralization in Broca's and Wernicke's areas, and structural measures of the arcuate fasciculus. Results revealed an effect of degree of hand preference on arcuate fasciculus structure, such that consistently-handed individuals, regardless of the direction of hand preference, demonstrated the most asymmetric arcuate fasciculus, with larger left versus right arcuate, as measured by DTI. Functional language lateralization in Wernicke's area, measured via fMRI, was related to arcuate fasciculus volume in consistent-left-handers only, and only in people who were not right hemisphere lateralized for language; given the small sample size for this finding, future investigation is warranted. Results suggest handedness degree may be an important variable to investigate in the context of neuroanatomical asymmetries.

Contributions to singing ability by the posterior portion of the superior temporal gyrus of the non-language-dominant hemisphere: first evidence from subdural cortical stimulation, Wada testing, and fMRI.

INTRODUCTION: Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electro-cortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity. METHODS: We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional magnetic resonance imaging (fMRI). Functional organization of singing ability compared to language ability was determined based on four regions-of-interest (ROIs): left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG). RESULTS: In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. Functional fMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the ROIs. CONCLUSION: Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients.

Threshold-independent functional MRI determination of language dominance: a validation study against clinical gold standards.

Functional MRI (fMRI) is often used for presurgical language lateralization. In the most common approach, a laterality index (LI) is calculated on the basis of suprathreshold voxels. However, strong dependencies between LI and threshold can diminish the effectiveness of this technique; in this study we investigated an original methodology that is independent of threshold. We compared this threshold-independent method against the common threshold-dependent method in 14 patients with epilepsy who underwent Wada testing. In addition, clinical results from electrocortical language mapping and postoperative language findings were used to assess the validity of the fMRI lateralization method. The threshold-dependent methodology yielded ambiguous or incongruent lateralization outcomes in 4 of 14 patients in the inferior frontal gyrus (IFG) and in 6 of 14 patients in the supramarginal gyrus (SMG). Conversely, the threshold-independent method yielded unambiguous lateralization in all the patients tested, and demonstrated lateralization outcomes incongruent with clinical standards in 2 of 14 patients in IFG and in 1 of 14 patients in SMG. This validation study demonstrates that the threshold-dependent LI calculation is prone to significant within-patient variability that could render results unreliable; the threshold-independent method can generate distinct LIs that are more concordant with gold standard clinical findings.

High b-value apparent diffusion-weighted images from CURVE-ball DTI.

PURPOSE: To investigate the utility of a proposed clinical diffusion imaging scheme for rapidly generating multiple b-value diffusion contrast in brain magnetic resonance imaging (MRI) with high signal-to-noise ratio (SNR). MATERIALS AND METHODS: Our strategy for efficient image acquisition relies on the invariance property of the diffusion tensor eigenvectors to b-value. A simple addition to the conventional diffusion tensor MR imaging (DTI) data acquisition scheme used for tractography yields diffusion-weighted images at twice and three times the conventional b-value. An example from a neurosurgical brain tumor is shown. Apparent diffusion-weighted (ADW) images were calculated for b-values 800, 1600, and 2400 s/mm(2), and a map of excess diffusive kurtosis was computed from the three ADWs. RESULTS: High b-value ADW images demonstrated decreased contrast between normal gray and white matter, while the heterogeneity and contrast of the lesion was emphasized relative to conventional b-value data. Kurtosis maps indicated the deviation from Gaussian diffusive behavior. CONCLUSION: DTI data with multiple b-values and good SNR can be acquired in clinically reasonable times. High b-value ADW images show increased contrast and add information to conventional DWI. Ambiguity in conventional b-value images over whether hyperintense signal results from abnormally low diffusion, or abnormally long T(2), is better resolved in high b-value images.

An intraoperative brain shift monitor using shear mode transcranial ultrasound: preliminary results.

OBJECTIVE: Various methods of intraoperative structural monitoring during neurosurgery are used to localize lesions after brain shift and to guide surgically introduced probes such as biopsy needles or stimulation electrodes. With its high temporal resolution, portability, and nonionizing mode of radiation, ultrasound has potential advantages over other existing imaging modalities for intraoperative monitoring, yet ultrasound is rarely used during neurosurgery largely because of the craniotomy requirement to achieve sufficiently useful signals. METHODS: Prompted by results from recent studies on transcranial ultrasound, a prototype device that aims to use the shear mode of transcranial ultrasound transmission for intraoperative monitoring was designed, constructed, and tested with 10 human participants. Magnetic resonance images were then obtained with the device spatially registered to the magnetic resonance imaging (MRI) reference coordinates. Peaks in both the ultrasound and MRI signals were identified and analyzed for both spatial localization and signal-to-noise ratio (SNR). RESULTS: The first results aimed toward validating the prototype device with MRI showed an excellent correlation (n = 38; R(2) = 0.9962) between the structural localization abilities of the two modalities. In addition, the overall SNR of the ultrasound backscatter signals (n = 38; SNR = 25.4 +/- 5.2 dB, mean +/- SD) was statistically equivalent to that of the MRI data (n = 38; SNR = 22.5 +/- 4.8 dB). CONCLUSIONS: A statistically significant correlation of localized intracranial structures between intraoperative transcranial ultrasound monitoring and MRI data was achieved with 10 human participants. We have shown and validated a prototype device incorporating transcranial shear mode ultrasound for clinical monitoring applications.

Comparison of blocked and event-related fMRI designs for pre-surgical language mapping.

Language functional magnetic resonance imaging (fMRI) is a promising non-invasive technique for pre-surgical planning in patients whose lesions are adjacent to or within critical language areas. Most language fMRI studies in patients use blocked experimental design. In this study, we compared a blocked design and a rapid event-related design with a jittered inter-stimulus-interval (ISI) (or stochastic design) for language fMRI in six healthy controls, and eight brain tumor patients, using a vocalized antonym generation task. Comparisons were based on visual inspection of fMRI activation maps and degree of language lateralization, both of which were assessed at a constant statistical threshold for each design. The results indicated a relatively high degree of discordance between the two task designs. In general, the event-related design provided maps with more robust activations in the putative language areas than the blocked design, especially for brain tumor patients. Our results suggest that the rapid event-related design has potential for providing comparable or even higher detection power over the blocked design for localizing language function in brain tumor patients, and therefore may be able to generate more sensitive language maps. More patient studies, and further investigation and optimization of language fMRI paradigms will be needed to determine the utility and validity of this approach for pre-surgical planning.

Resolving crossings in the corticospinal tract by two-tensor streamline tractography: Method and clinical assessment using fMRI.

An inherent drawback of the traditional diffusion tensor model is its limited ability to provide detailed information about multidirectional fiber architecture within a voxel. This leads to erroneous fiber tractography results in locations where fiber bundles cross each other. This may lead to the inability to visualize clinically important tracts such as the lateral projections of the corticospinal tract. In this report, we present a deterministic two-tensor eXtended Streamline Tractography (XST) technique, which successfully traces through regions of crossing fibers. We evaluated the method on simulated and in vivo human brain data, comparing the results with the traditional single-tensor and with a probabilistic tractography technique. By tracing the corticospinal tract and correlating with fMRI-determined motor cortex in both healthy subjects and patients with brain tumors, we demonstrate that two-tensor deterministic streamline tractography can accurately identify fiber bundles consistent with anatomy and previously not detected by conventional single-tensor tractography. When compared to the dense connectivity maps generated by probabilistic tractography, the method is computationally efficient and generates discrete geometric pathways that are simple to visualize and clinically useful. Detection of crossing white matter pathways can improve neurosurgical visualization of functionally relevant white matter areas.

Fieldmap-free retrospective registration and distortion correction for EPI-based functional imaging.

We describe a method for correcting the distortions present in echo planar images (EPI) and registering the EPI to structural MRI. A fieldmap is predicted from an air / tissue segmentation of the MRI using a perturbation method and subsequently used to unwarp the EPI data. Shim and other missing parameters are estimated by registration. We obtain results that are similar to those obtained using fieldmaps, however neither fieldmaps, nor knowledge of shim coefficients is required.

Group independent component analysis of language fMRI from word generation tasks.

Language fMRI has been used to study brain regions involved in language processing and has been applied to pre-surgical language mapping. However, in order to provide clinicians with optimal information, the sensitivity and specificity of language fMRI needs to be improved. Type II error of failing to reach statistical significance when the language activations are genuinely present may be particularly relevant to pre-surgical planning, by falsely indicating low surgical risk in areas where no activations are shown. Furthermore, since the execution of language paradigms involves cognitive processes other than language function per se, the conventional general linear model (GLM) method may identify non-language-specific activations. In this study, we assessed an exploratory approach, independent component analysis (ICA), as a potential complementary method to the inferential GLM method in language mapping applications. We specifically investigated whether this approach might reduce type II error as well as generate more language-specific maps. Fourteen right-handed healthy subjects were studied with fMRI during two word generation tasks. A similarity analysis across tasks was proposed to select components of interest. Union analysis was performed on the language-specific components to increase sensitivity, and conjunction analysis was performed to identify language areas more likely to be essential. Compared with GLM, ICA identified more activated voxels in the putative language areas, and signals from other sources were isolated into different components. Encouraging results from one brain tumor patient are also presented. ICA may be used as a complementary tool to GLM in improving pre-surgical language mapping.

Compensation of geometric distortion effects on intraoperative magnetic resonance imaging for enhanced visualization in image-guided neurosurgery.

OBJECTIVE: Preoperative magnetic resonance imaging (MRI), functional MRI, diffusion tensor MRI, magnetic resonance spectroscopy, and positron-emission tomographic scans may be aligned to intraoperative MRI to enhance visualization and navigation during image-guided neurosurgery. However, several effects (both machine- and patient-induced distortions) lead to significant geometric distortion of intraoperative MRI. Therefore, a precise alignment of these image modalities requires correction of the geometric distortion. We propose and evaluate a novel method to compensate for the geometric distortion of intraoperative 0.5-T MRI in image-guided neurosurgery. METHODS: In this initial pilot study, 11 neurosurgical procedures were prospectively enrolled. The scheme used to correct the geometric distortion is based on a nonrigid registration algorithm introduced by our group. This registration scheme uses image features to establish correspondence between images. It estimates a smooth geometric distortion compensation field by regularizing the displacements estimated at the correspondences. A patient-specific linear elastic material model is used to achieve the regularization. The geometry of intraoperative images (0.5 T) is changed so that the images match the preoperative MRI scans (3 T). RESULTS: We compared the alignment between preoperative and intraoperative imaging using 1) only rigid registration without correction of the geometric distortion, and 2) rigid registration and compensation for the geometric distortion. We evaluated the success of the geometric distortion correction algorithm by measuring the Hausdorff distance between boundaries in the 3-T and 0.5-T MRIs after rigid registration alone and with the addition of geometric distortion correction of the 0.5-T MRI. Overall, the mean magnitude of the geometric distortion measured on the intraoperative images is 10.3 mm with a minimum of 2.91 mm and a maximum of 21.5 mm. The measured accuracy of the geometric distortion compensation algorithm is 1.93 mm. There is a statistically significant difference between the accuracy of the alignment of preoperative and intraoperative images, both with and without the correction of geometric distortion (P < 0.001). CONCLUSION: The major contributions of this study are 1) identification of geometric distortion of intraoperative images relative to preoperative images, 2) measurement of the geometric distortion, 3) application of nonrigid registration to compensate for geometric distortion during neurosurgery, 4) measurement of residual distortion after geometric distortion correction, and 5) phantom study to quantify geometric distortion.

Object naming is a more sensitive measure of speech localization than number counting: Converging evidence from direct cortical stimulation and fMRI.

Using direct cortical stimulation to map language function during awake craniotomy is a well-described and useful technique. However, the optimum neuropsychological tasks to use have not been detailed. We used both functional MRI (fMRI) and direct cortical stimulation to compare the sensitivity of two behavioral paradigms, number counting and object naming, in the demonstration of eloquent cortical language areas. Fifteen patients with left hemisphere lesions and seven healthy control subjects participated. Patients had both preoperative fMRI at 3 T and direct cortical stimulation. Patients and controls performed object naming and number counting during fMRI at 3 T. Laterality indices were calculated from the fMRI maps for the Number-counting>Object-naming and Object-naming>Number-counting contrasts. The same number-counting and object-naming paradigms were tested during awake craniotomy and assessed for sensitivity to speech disruption. In all patients during intraoperative cortical stimulation, speech disruption occurred at more sites during object naming than during number counting. Subtle speech errors were only elicited with the object-naming paradigm, whereas only speech arrest and/or hypophonia were measured using the number counting paradigm. In both patients and controls, fMRI activation maps demonstrated greater left lateralization for object naming as compared to number counting in both frontal and temporal language areas. Number counting resulted in a more bihemispheric distribution of activations than object naming. Both cortical stimulation testing and fMRI suggest that automated speech tasks such as number counting may not fully engage putative language networks and therefore are not optimal for language localization for surgical planning.

Non-rigid alignment of pre-operative MRI, fMRI, and DT-MRI with intra-operative MRI for enhanced visualization and navigation in image-guided neurosurgery.

OBJECTIVE: The usefulness of neurosurgical navigation with current visualizations is seriously compromised by brain shift, which inevitably occurs during the course of the operation, significantly degrading the precise alignment between the pre-operative MR data and the intra-operative shape of the brain. Our objectives were (i) to evaluate the feasibility of non-rigid registration that compensates for the brain deformations within the time constraints imposed by neurosurgery, and (ii) to create augmented reality visualizations of critical structural and functional brain regions during neurosurgery using pre-operatively acquired fMRI and DT-MRI. MATERIALS AND METHODS: Eleven consecutive patients with supratentorial gliomas were included in our study. All underwent surgery at our intra-operative MR imaging-guided therapy facility and have tumors in eloquent brain areas (e.g. precentral gyrus and cortico-spinal tract). Functional MRI and DT-MRI, together with MPRAGE and T2w structural MRI were acquired at 3 T prior to surgery. SPGR and T2w images were acquired with a 0.5 T magnet during each procedure. Quantitative assessment of the alignment accuracy was carried out and compared with current state-of-the-art systems based only on rigid registration. RESULTS: Alignment between pre-operative and intra-operative datasets was successfully carried out during surgery for all patients. Overall, the mean residual displacement remaining after non-rigid registration was 1.82 mm. There is a statistically significant improvement in alignment accuracy utilizing our non-rigid registration in comparison to the currently used technology (p<0.001). CONCLUSIONS: We were able to achieve intra-operative rigid and non-rigid registration of (1) pre-operative structural MRI with intra-operative T1w MRI; (2) pre-operative fMRI with intra-operative T1w MRI, and (3) pre-operative DT-MRI with intra-operative T1w MRI. The registration algorithms as implemented were sufficiently robust and rapid to meet the hard real-time constraints of intra-operative surgical decision making. The validation experiments demonstrate that we can accurately compensate for the deformation of the brain and thus can construct an augmented reality visualization to aid the surgeon.

Functional MRI of memory in the hippocampus: Laterality indices may be more meaningful if calculated from whole voxel distributions.

Lateralization of memory by functional MRI (fMRI) may be helpful for surgical planning related to the medial temporal lobe (MTL). Most fMRI memory studies have calculated lateralization indices (LI) in the MTL from suprathreshold voxels only, but the selection of threshold remains highly arbitrary. We hypothesized that LIs could be reliably extracted from the distribution of voxels encompassing all positive T statistical values, each weighted by their own statistical significance. We also hypothesized that patient LIs that are two or more standard deviations (SD) away from the control group mean LI may be more clinically relevant than LIs that are not compared to control group. Thirteen healthy subjects had memory fMRI, and five epilepsy patients had both fMRI and the intracarotid amobarbital procedure (IAP). The fMRI task consisted of encoding patterns, scenes, and words. We found that normal subjects' LIs extracted from whole weighted statistical distributions tended to lateralize to the left for words, to the right for patterns, and intermediately for scenes, consistent with previous research. Weighted LIs were less variable than those calculated from suprathreshold voxels only. Using this approach, all patients had fMRI memory lateralizations consistent with IAP results. The weighted LIs provided a more clear-cut distinction of patients from the normal group (in terms of SDs from the group mean) than the suprathreshold voxel count approach. Our results suggest that using weighted distributions can be a useful strategy for assessing memory lateralization by fMRI in the MTL.

Integrated image- and function-guided surgery in eloquent cortex: a technique report.

The ability to effectively identify eloquent cortex in close proximity to brain tumours is a critical component of surgical planning prior to resection. The use of electrocortical stimulation testing (ECS) during awake neurosurgical procedures remains the gold standard for mapping functional areas, yet the preoperative use of non-invasive brain imaging techniques such as fMRI are gaining popularity as supplemental surgical planning tools. In addition, the intraoperative three-dimensional display of fMRI findings co-registered to structural imaging data maximizes the utility of the preoperative mapping for the surgeon. Advances in these techniques have the potential to limit the size and duration of craniotomies as well as the strain placed on the patient, but more research accurately demonstrating their efficacy is required. In this paper, we demonstrate the integration of preoperative fMRI within a neuronavigation system to aid in surgical planning, as well as the integration of these fMRI data with intraoperative ECS mapping results into a three-dimensional dataset for the purpose of cross-validation.

FunctionalMRI memory Mapping for epilepsy surgery planning: a case report

Functional evaluation of memory lateralization can have an impact of epilepsy surgery for mesial temporal lobe (MTL)epilepsy. Functional MRI (fMRI) may provide non-invasive method to assist in the determinations of memory dominance. FMRI based memory mapping, however, is still not strainghforward and determining lateralization can be difficult for a number of reasons. One oustanding question relates to the influence of material type on MTL activation. To improve pre-operative memory lateralization evaluation using an event-related fMRI paradigm. This approach was designed to take into account succeful encoding and material type. We describe here the case of a patient with MTL epilepsy who inderwent memory mapping using this new functional MRI design. For each stimulus modality, we generated maps and calculated the lateralization of the activations. The patterns encoding task was associated with the most righ-lateralized MTL activity, whereas word encoding was the brain region for different stimulus modalities that follow the overall pattern found in our previous blocked-design studies. The mapping in this case was concordant with the structural imaging and electrophysiological findings

Asymmetry of subinsular anisotropy by in vivo diffusion tensor imaging.

The cortical regions specialized in speech-language exhibit a left-right asymmetry, e.g., a larger cortical size in the left auditory cortex and Wernicke's area. The possibility of developmental asymmetry in axonal fibers interconnecting speech-language cortical areas can be investigated by in vivo diffusion tensor imaging. Fifteen right-handed native English speakers showed a markedly significant asymmetry (P < 0. 0005) in the relative anisotropy of water diffusion in the subinsular white matter, greater on the left. Additionally, the first principal diffusivity was greater and the second and third principal diffusivities were smaller on the left than right side. These results suggest the subinsular axonal structures developed differently between the left and right sides. A possible association between the hemispheric specialization in language and speech and the subinsular axonal fiber development is discussed.