Optic radiation fiber tractography in glioma patients based on high angular resolution diffusion imaging with compressed sensing compared with diffusion tensor imaging - initial experience.

OBJECTIVE: Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI). However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI) which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS) techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine. METHODS: Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR), underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS. RESULTS: HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract. CONCLUSIONS: Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery.

Reconstruction of white matter tracts via repeated deterministic streamline tracking--initial experience.

Diffusion Tensor Imaging (DTI) and fiber tractography are established methods to reconstruct major white matter tracts in the human brain in-vivo. Particularly in the context of neurosurgical procedures, reliable information about the course of fiber bundles is important to minimize postoperative deficits while maximizing the tumor resection volume. Since routinely used deterministic streamline tractography approaches often underestimate the spatial extent of white matter tracts, a novel approach to improve fiber segmentation is presented here, considering clinical time constraints. Therefore, fiber tracking visualization is enhanced with statistical information from multiple tracking applications to determine uncertainty in reconstruction based on clinical DTI data. After initial deterministic fiber tracking and centerline calculation, new seed regions are generated along the result's midline. Tracking is applied to all new seed regions afterwards, varying in number and applied offset. The number of fibers passing each voxel is computed to model different levels of fiber bundle membership. Experimental results using an artificial data set of an anatomical software phantom are presented, using the Dice Similarity Coefficient (DSC) as a measure of segmentation quality. Different parameter combinations were classified to be superior to others providing significantly improved results with DSCs of 81.02%±4.12%, 81.32%±4.22% and 80.99%±3.81% for different levels of added noise in comparison to the deterministic fiber tracking procedure using the two-ROI approach with average DSCs of 65.08%±5.31%, 64.73%±6.02% and 65.91%±6.42%. Whole brain tractography based on the seed volume generated by the calculated seeds delivers average DSCs of 67.12%±0.86%, 75.10%±0.28% and 72.91%±0.15%, original whole brain tractography delivers DSCs of 67.16%, 75.03% and 75.54%, using initial ROIs as combined include regions, which is clearly improved by the repeated fiber tractography method.

Fiber tractography based on diffusion tensor imaging compared with high-angular-resolution diffusion imaging with compressed sensing: initial experience.

BACKGROUND: The most frequently used method for fiber tractography based on diffusion tensor imaging (DTI) is associated with restrictions in the resolution of crossing or kissing fibers and in the vicinity of tumor or edema. Tractography based on high-angular-resolution diffusion imaging (HARDI) is capable of overcoming this restriction. With compressed sensing (CS) techniques, HARDI acquisitions with a smaller number of directional measurements can be used, thus enabling the use of HARDI-based fiber tractography in clinical practice. OBJECTIVE: To investigate whether HARDI+CS-based fiber tractography improves the display of neuroanatomically complex pathways and in areas of disturbed diffusion properties. METHODS: Six patients with gliomas in the vicinity of language-related areas underwent 3-T magnetic resonance imaging including a diffusion-weighted data set with 30 gradient directions. Additionally, functional magnetic resonance imaging for cortical language sites was obtained. Fiber tractography was performed with deterministic streamline algorithms based on DTI using 3 different software platforms. Additionally, tractography based on reconstructed diffusion signals using HARDI+CS was performed. RESULTS: HARDI+CS-based tractography displayed more compact fiber bundles compared with the DTI-based results in all cases. In 3 cases, neuroanatomically plausible fiber bundles were displayed in the vicinity of tumor and peritumoral edema, which could not be traced on the basis of DTI. The curvature around the sylvian fissure was displayed properly in 6 cases and in only 2 cases with DTI-based tractography. CONCLUSION: HARDI+CS seems to be a promising approach for fiber tractography in clinical practice for neuroanatomically complex fiber pathways and in areas of disturbed diffusion, overcoming the problem of long acquisition times.

Reversible cortical blindness and internuclear ophthalmoplegia after neurosurgical operation: case report and review of the literature.

BACKGROUND: The reversible posterior leukoencephalopathy (RPL) syndrome with typical vasogenic edema in the occipital lobe and associated cortical blindness is a rare finding; however, the brainstem variant is even more infrequent. Etiologies discussed include blood pressure dysregulations, renal failure, or immunosuppression. PATIENT: A 63-year-old man with the characteristic radiographic findings of RPL syndrome presented with reversible cortical blindness and internuclear ophthalmoplegia (INO) after resection of an infratentorial hemangiopericytoma. The patient postoperatively presented with diplopia and mental status alterations followed by visual loss; these symptoms completely recovered within a few days. Fluid-attenuated inversion recovery-, and T2-weighted magnetic resonance imaging (MRI) revealed bilateral hyperintense lesions not only in the white matter of the parieto-occipital region but also in the rostral paramedian mesencephalon and pons. CONCLUSIONS: We hypothesize that the patient had an RPL, coincidentally in classic-, and brainstem localization, caused by perioperative fluctuations of blood pressure.

Contrast-enhanced ultrasound ventriculography.

BACKGROUND: During external ventricular drainage (EVD) weaning, cranial computed tomography (cCT) is necessary to evaluate ventricle width. Because intrahospital transfer of critically ill patients is associated with higher mortality, bedside techniques are necessary to evaluate ventricle width. Transcranial sonography is able to show the ventricles in patients with sufficient temporal acoustic window. Contrast-enhanced ultrasound (CEUS) is able to overcome the limitations of insufficient insonation. OBJECTIVE: We demonstrate the feasibility of bedside transcranial CEUS ventriculography to measure ventricles and verify the passage of cerebrospinal fluid (CSF) through the foramen of Magendie into the subarachnoid space during EVD weaning in critically ill patients. METHODS: Six patients were examined by transcranial and transnuchal CEUS. Harmonic imaging with low mechanical index was used. One milliliter of an ultrasound contrast agent was administered via EVD line. Comparison with the cCT scans at the time of discharge was used to confirm CEUS-ventriculography results. RESULTS: Ventricles were visualized in all patients. CSF transmission via the foramen of Magendie was demonstrated in 5 patients. Mean ventricle width (centimeters) was 0.67 (CEUS) vs 0.73 (cCT) (standard deviation 0.43, 0.45, P = .116) [third ventricle], 0.88 vs 1.02 (0.28, 0.22, P = .055) [fourth ventricle], 1.40 vs 1.37 (0.56, 0.54, P = .620) [left lateral ventricle], 1.37 vs 1.37 (0.55, 0.54, P = .952) [right lateral ventricle], 2.33 vs 2.23 (0.51, 0.58, P = .169) [left anterior horn], and 2.25 vs 2.07 (0.56, 0.64, P = .204) [right anterior horn]. Mean duration for CEUS ventriculography was 3:15 minutes. CONCLUSION: CEUS ventriculography is an effective bedside procedure in critically ill patients with EVD. CEUS allows measurement of ventricle width, ventricle communication, and CSF transfer to the subarachnoidal space through the cisternal foramina.

Brain shift compensation and neurosurgical image fusion using intraoperative MRI: current status and future challenges.

Navigation systems are commonly used in neurosurgical operating theaters. Generally, they either rely on the use of preoperative or intraoperative image data. Using preoperative image data, the phenomenon of brain shift contributes most to errors, in addition to various other sources of decreased reliability, such as image-related errors or registration inaccuracy. Updating navigation after intraoperative magnetic resonance imaging (iMRI) serves as immediate feedback on the surgical result and furthermore compensates for the effects of brain shift. Together with an integration of functional data in the navigation such as diffusion tensor imaging (DTI)-based fiber tracking or functional MRI, there is evidence that iMRI contributes to maximize extent of resection in glioma surgery with a preservation of neurological function. The following article summarizes the work flow and clinical impact of iMRI and functional navigation, as well as current problems and possible solutions.

Intraoperative visualization of fiber tracking based reconstruction of language pathways in glioma surgery.

BACKGROUND: For neuroepithelial tumors, the surgical goal is maximum resection with preservation of neurological function. This is contributed to by intraoperative magnetic resonance imaging (iMRI) combined with multimodal navigation. OBJECTIVE: We evaluated the contribution of diffusion tensor imaging (DTI)-based fiber tracking of language pathways with 2 different algorithms (tensor deflection, connectivity analysis [CA]) integrated in the navigation on the surgical outcome. METHODS: We evaluated 32 patients with neuroepithelial tumors who underwent surgery with DTI-based fiber tracking of language pathways integrated in neuronavigation. The tensor deflection algorithm was routinely used and its results intraoperatively displayed in all cases. The CA algorithm was furthermore evaluated in 23 cases. Volumetric assessment was performed in pre- and intraoperative MR images. To evaluate the benefit of fiber tractography, language deficits were evaluated pre- and postoperatively and compared with the volumetric analysis. RESULTS: Final gross-total resection was performed in 40.6% of patients. Absolute tumor volume was reduced from 55.33 ± 63.77 cm(3) to 20.61 ± 21.67 cm(3) in first iMRI resection control, to finally 11.56 ± 21.92 cm(3) (P < .01). Fiber tracking of the 2 algorithms showed a deviation of the displayed 3D objects by <5 mm. In long-term follow-up only 1 patient (3.1%) had a persistent language deficit. CONCLUSION: Intraoperative visualization of language-related cortical areas and the connecting pathways with DTI-based fiber tracking can be successfully performed and integrated in the navigation system. In a setting of intraoperative high-field MRI this contributes to maximum tumor resection with low postoperative morbidity.

Correlation of the extent of tumor volume resection and patient survival in surgery of glioblastoma multiforme with high-field intraoperative MRI guidance.

Extent of resection (EOR) still remains controversial in therapy of glioblastoma multiforme (GBM). However, an increasing number of studies favor maximum EOR as being associated with longer patient survival. One hundred thirty-five GBM patients underwent tumor resection aided by 1.5T intraoperative MRI (iMRI) and integrated multimodal navigation. Tumor volume was quantified by manual segmentation. The influences of EOR, patient age, recurrent tumor, tumor localization, and gender on survival time were examined. Intraoperative MRI detected residual tumor volume in 88 patients. In 19 patients surgery was continued; further resection resulted in final gross total resection (GTR) for 9 patients (GTR increased from 47 [34.80%] to 56 [41.49%] patients). Tumor volumes were significantly reduced from 34.25 ± 23.68% (first iMRI) to 1.22 ± 16.24% (final iMRI). According to Kaplan-Meier estimates, median survival was 14 months (95% confidence interval [CI]: 11.7-16.2) for EOR ≥ 98% and 9 months (95% CI: 7.4-10.5) for EOR <98% (P< .0001); it was 9 months (95% CI: 7.3-10.7) for patients ≥ 65 years and 12 months (95% CI: 8.4-15.6) for patients <65 years (P < .05). Multivariate analysis showed a hazard ratio of 0.39 (95% CI: 0.24-0.63; P = .001) for EOR ≥ 98% and 0.61 (95% CI: 0.38-0.97; P < .05) for patient age <65 years. To our knowledge, this is the largest study including correlation of iMRI, tumor volumetry, and survival time. We demonstrate that navigation guidance and iMRI significantly contribute to optimal EOR with low postoperative morbidity, where EOR ≥ 98% and patient age <65 years are associated with significant survival advantages. Thus, maximum EOR should be the surgical goal in GBM surgery while preserving neurological function.

Quantification of glioma removal by intraoperative high-field magnetic resonance imaging: an update.

BACKGROUND: The beneficial role of the extent of resection (EOR) in glioma surgery in correlation to increased survival remains controversial. However, common literature favors maximum EOR with preservation of neurological function, which is shown to be associated with a significantly improved outcome. OBJECTIVE: In order to obtain a maximum EOR, it was examined whether high-field intraoperative magnetic resonance imaging (iMRI) combined with multimodal navigation contributes to a significantly improved EOR in glioma surgery. METHODS: Two hundred ninety-three glioma patients underwent craniotomy and tumor resection with the aid of intraoperative 1.5 T MRI and integrated multimodal navigation. In cases of remnant tumor, an update of navigation was performed with intraoperative images. Tumor volume was quantified pre- and intraoperatively by segmentation of T2 abnormality in low-grade and contrast enhancement in high-grade gliomas. RESULTS: In 25.9% of all cases examined, additional tumor mass was removed as a result of iMRI. This led to complete tumor resection in 20 cases, increasing the rate of gross-total removal from 31.7% to 38.6%. In 56 patients, additional but incomplete resection was performed because of the close location to eloquent brain areas. Volumetric analysis showed a significantly (P < .01) reduced mean percentage of tumor volume following additional further resection after iMRI from 33.5% ± 25.1% to 14.7% ± 23.3% (World Health Organization [WHO] grade I, 32.8% ± 21.9% to 6.1% ± 18.8%; WHO grade II, 24.4% ± 25.1% to 10.8% ± 11.0%; WHO grade III, 35.1% ± 27.3% to 24.8% ± 26.3%; WHO grade IV, 34.2% ± 23.7% to 1.2% ± 16.2%). CONCLUSION: MRI in conjunction with multimodal navigation and an intraoperative updating procedure enlarges tumor-volume reduction in glioma surgery significantly without higher postoperative morbidity.

Boundary estimation of fiber bundles derived from diffusion tensor images.

PURPOSE: Diffusion tensor imaging (DTI) is a non-invasive imaging technique that allows estimating the location of white matter tracts based on the measurement of water diffusion properties. Using DTI data, the fiber bundle boundary can be determined to gain information about eloquent structures, which is of major interest for neurosurgical interventions. In this paper, a novel approach for boundary estimation is presented. METHODS: DTI in combination with diverse segmentation algorithms allows estimating the position and course of fiber tracts in the human brain. For additional information about the expansion of the fiber bundle, the introduced iterative approach uses the centerline of a tracked fiber bundle between two regions of interest (ROI). After sampling along this centerline, rays are sent out radially, discrete 2D contours are calculated, and the fiber bundle boundary is estimated in a stepwise manner. For this purpose, each ray is analyzed using several criteria, including anisotropy parameters and angle parameters, to find the boundary point. RESULTS: The novel method for automatically calculating the boundaries has been applied to several artificially generated DTI datasets. Multiple parameters were varied: number of rays per plane, sampling rate and sampled points along the rays. For the DTI data used in the experiments, the method yielded a dice similarity coefficient (DSC) between 74.7 and 91.5%. CONCLUSIONS: In this paper, a novel approach to retrieve significant information about the fiber bundle boundary from DTI data is presented. The method is a contribution to gather important knowledge about high-risk structures in neurosurgical interventions.

The wolf is crying in the operating room: patient monitor and anesthesia workstation alarming patterns during cardiac surgery.

BACKGROUND: Vital sign monitors and ventilator/anesthesia workstations are equipped with multiple alarms to improve patient safety. A high number of false alarms can lead to a "crying wolf" phenomenon with consecutively ignored critical situations. Systematic data on alarm patterns and density in the perioperative phase are missing. Our objective of this study was to characterize the patterns of alarming of a commercially available patient monitor and a ventilator/anesthesia workstation during elective cardiac surgery. METHODS: We performed a prospective, observational study in 25 consecutive elective cardiac surgery patients. In all patients, identically fixed alarm settings were used. All incoming patient data and all alarms from the patient monitor and the anesthetic workstation were digitally recorded. Additionally, the anesthesia workplace was videotaped from 2 different angles to allow retrospective annotation and correlation of alarms with the clinical situation and assessment of the anesthesiologists' reaction to the alarms. RESULTS: Of the 8975 alarms, 7556 were hemodynamic alarms and 1419 were ventilatory alarms. For each procedure, 359 ± 158 alarms were recorded, representing a mean density of alarms of 1.2/minute. CONCLUSION: Approximately 80% of the total 8975 alarms had no therapeutic consequences. Implementation of procedure-specific settings and optimization in artifact and technical alarm detection could improve patient surveillance and safety.

Multimodal navigation integrated with imaging.

Intraoperative high-field MRI in combination and close integration with microscope-based navigation serving as a common interface for the presentation of multimodal data in the surgical field seems to be one of the most promising surgical setups allowing avoiding unwanted tumor remnants while preserving neurological function. Multimodal navigation integrates standard anatomical, structural, functional, and metabolic data. Navigation achieves visualizing the initial extent of a lesion with the concomitant identification of neighboring eloquent brain structures, as well as, providing a tool for a direct correlation of histology and multimodal data. With the help of intraoperative imaging navigation data can be updated, so that brain shift can be compensated for and initially missed tumor remnants can be localized reliably.

Ultrasound active nanoscaled lipid formulations for thrombus lysis.

In the present study, we investigated the sonothrombolytic effect of new nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound. Human blood clots of 1 ml were incubated with 1 µl of the different lipid dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available ultrasound contrast agent SonoVue®. Clots were stored for 3 days at 5 °C to obtain maximal clot retraction and lytic resistance. Each clot weight was determined before and after continuous insonation for 1h of insonation at 1.4 MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial blood pressure. There were no significant differences in thrombus weight before insonation. All nanoscaled formulations and SonoVue® were able to reduce thrombus weight compared to the weight loss of clots that were not insonated but kept under pressure for one hour (p < 0.001). We found a highly significant weight reduction with DSPC/PEG40S compared to SonoVue® (p = 0.007). Nanoscaled DSPC/PEG40S dispersion could be a promising formulation in ultrasound enhanced thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial parameter in fragmentation of thrombus architecture. Further studies of physicochemical properties of DSPC/PEG40S are necessary to corroborate our hypothesis.

Updating navigation with intraoperative image data.

OBJECTIVES: To localize overlooked tumor remnants by updating navigation with intraoperative magnetic resonance imaging compensating for the effects of brain shift. METHODS: In 112 patients among 805 patients that were investigated by combined use of intraoperative high-field (1.5 T) magnetic resonance imaging and navigation, mostly glioma cases (n = 85), an update of the navigation was performed. Intraoperative image data were rigidly registered with the preoperative image data, the tumor remnant was segmented, and then the initial patient registration was restored so that the registration coordinate system of the preoperative image data was applied on the intraoperative images, allowing navigation updating without intraoperative patient re-registration. RESULTS: Navigation could be updated reliably in all cases. Potential positional shifting impairing the initial update strategy was observed only in 2 cases so that a patient re-registration was necessary. The target registration error of the initial patient registration was 1.33 +/- 0.63 mm, and registration of preoperative and intraoperative images could be performed with high accuracy, as proven by landmark checks. Updating of navigation resulted in increased resections or correction of a catheter position or biopsy sampling site in 94%. In the remaining 7 patients, the intraoperative images were used for correlation with the surgical site but without changing the surgical strategy. CONCLUSIONS: Navigation can be reliably updated with intraoperative image data without repeated patient registration, facilitating the update procedure. Updated navigation allows achieving enlarged resections and compensates for the effects of brain shift.

The stem cell marker prominin-1/CD133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying central nervous system disease.

Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring neurological diseases. The CSF proteins used so far for diagnostic purposes (except for those associated with whole cells) are soluble. Here, we show that human CSF contains specific membrane particles that carry prominin-1/CD133, a neural stem cell marker implicated in brain tumors, notably glioblastoma. Differential and equilibrium centrifugation and detergent solubility analyses showed that these membrane particles were similar in physical properties and microdomain organization to small membrane vesicles previously shown to be released from neural stem cells in the mouse embryo. The levels of membrane particle-associated prominin-1/CD133 declined during childhood and remained constant thereafter, with a remarkably narrow range in healthy adults. Glioblastoma patients showed elevated levels of membrane particle-associated prominin-1/CD133, which decreased dramatically in the final stage of the disease. Hence, analysis of CSF for membrane particles carrying the somatic stem cell marker prominin-1/CD133 offers a novel approach for studying human central nervous system disease.