Eduard Voormolen

Association of schizophrenia in 22q11.2 deletion syndrome and gray matter volumetric deficits in the superior temporal gyrus.

OBJECTIVE Individuals with 22q11.2 deletion syndrome are known to be at high risk of developing schizophrenia. Previous imaging studies have provided limited data on the relation of schizophrenia expression in 22q11.2 deletion syndrome to specific regional brain volumetric changes. The authors hypothesized that the main structural brain finding associated with schizophrenia expression in 22q11.2 deletion syndrome, as for schizophrenia in the general population, would be gray matter volumetric deficits, especially in the temporal lobes. METHOD MR brain images from 29 patients with 22q11.2 deletion syndrome and schizophrenia and 34 comparison subjects with 22q11.2 deletion syndrome and no history of psychosis were analyzed using a voxel-based morphometry method that also yielded volumes for related region-of-interest analyses. The authors compared data from the two groups using an analysis of covariance model correcting for total intracranial volume, age, sex, IQ, and history of congenital cardiac defects. The false discovery rate threshold was set at 0.05 to account for multiple comparisons. RESULTS Voxel-based morphometry analyses identified significant gray matter reductions in the left superior temporal gyrus (Brodmanns area 22) in the schizophrenia group. There were no significant between-group differences in white matter or CSF volumes. Region-of-interest analyses showed significant bilateral gray matter volume reductions in the temporal lobes and superior temporal gyri in the schizophrenia group. CONCLUSIONS The structural brain expression of schizophrenia associated with the highly penetrant 22q11.2 deletion involves lower gray matter volumes in temporal lobe regions. These structural MRI findings in a 22q11.2 deletion syndrome form of schizophrenia are consistent with those from studies involving schizophrenia samples from the general population. The results provide further support for 22q11.2 deletion syndrome as a genetic subtype and as a useful neurodevelopmental model of schizophrenia.

Skull base tumor model

OBJECT Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training. METHODS Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback. RESULTS All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible achievable score where the evaluator strongly agreed with the proposed factor). Individual components had scores at or above 80% (except for 1). The only score that was below 80% was related to radiographic visibility of the model for adequate surgical planning (score of 74%). The highest score was given to usefulness in neurosurgical training (98%). CONCLUSIONS The skull base tumor model is an effective tool to provide more practice in preoperative planning and technical skills.

Voxel-based morphometry and automated lobar volumetry: The trade-off between spatial scale and statistical correction

Voxel-based morphometry (VBM) and automated lobar region of interest (ROI) volumetry are comprehensive and fast methods to detect differences in overall brain anatomy on magnetic resonance images. However, VBM and automated lobar ROI volumetry have detected dissimilar gray matter differences within identical image sets in our own experience and in previous reports. To gain more insight into how diverging results arise and to attempt to establish whether one method is superior to the other, we investigated how differences in spatial scale and in the need to statistically correct for multiple spatial comparisons influence the relative sensitivity of either technique to group differences in gray matter volumes. We assessed the performance of both techniques on a small dataset containing simulated gray matter deficits and additionally on a dataset of 22q11-deletion syndrome patients with schizophrenia (22q11DS-SZ) vs. matched controls. VBM was more sensitive to simulated focal deficits compared to automated ROI volumetry, and could detect global cortical deficits equally well. Moreover, theoretical calculations of VBM and ROI detection sensitivities to focal deficits showed that at increasing ROI size, ROI volumetry suffers more from loss in sensitivity than VBM. Furthermore, VBM and automated ROI found corresponding GM deficits in 22q11DS-SZ patients, except in the parietal lobe. Here, automated lobar ROI volumetry found a significant deficit only after a smaller sub-region of interest was employed. Thus, sensitivity to focal differences is impaired relatively more by averaging over larger volumes in automated ROI methods than by the correction for multiple comparisons in VBM. These findings indicate that VBM is to be preferred over automated lobar-scale ROI volumetry for assessing gray matter volume differences between groups.

Amide proton transfer (APT) imaging of brain tumors at 7 T : The role of tissue water T1 -Relaxation properties

To provide insight into the effect of water T1 relaxation (T1wat) on amide proton transfer (APT) contrast in tumors. Three different metrics of APT contrast—magnetization transfer ratio (MTRRex), relaxation‐compensated MTRRex (AREX), and traditional asymmetry (MTRasym)—were compared in normal and tumor tissues in a variety of intracranial tumors at 7 Tesla (T).

Validation of exposure visualization and audible distance emission for navigated temporal bone drilling in phantoms.

Background A neuronavigation interface with extended function as compared with current systems was developed to aid during temporal bone surgery. The interface, named EVADE, updates the prior anatomical image and visualizes the bone drilling process virtually in real-time without need for intra-operative imaging. Furthermore, EVADE continuously calculates the distance from the drill tip to segmented temporal bone critical structures (e.g. the sigmoid sinus and facial nerve) and produces audiovisual warnings if the surgeon drills in too close vicinity. The aim of this study was to evaluate the accuracy and surgical utility of EVADE in physical phantoms. Methodology/Principal Findings We performed 228 measurements assessing the position accuracy of tracking a navigated drill in the operating theatre. A mean target registration error of 1.33±0.61 mm with a maximum error of 3.04 mm was found. Five neurosurgeons each drilled two temporal bone phantoms, once using EVADE, and once using a standard neuronavigation interface. While using standard neuronavigation the surgeons damaged three modeled temporal bone critical structures. No structure was hit by surgeons utilizing EVADE. Surgeons felt better orientated and thought they had improved tumor exposure with EVADE. Furthermore, we compared the distances between surface meshes of the virtual drill cavities created by EVADE to actual drill cavities: average maximum errors of 2.54±0.49 mm and −2.70±0.48 mm were found. Conclusions/Significance These results demonstrate that EVADE gives accurate feedback which reduces risks of harming modeled critical structures compared to a standard neuronavigation interface during temporal bone phantom drilling.

Determination of a facial nerve safety zone for navigated temporal bone surgery.

BACKGROUND: Transtemporal approaches require surgeons to drill the temporal bone to expose target lesions while avoiding the critical structures within it, such as the facial nerve and other neurovascular structures. We envision a novel protective neuronavigation system that continuously calculates the drill tip-to-facial nerve distance intraoperatively and produces audiovisual warnings if the surgeon drills too close to the facial nerve. Two major problems need to be solved before such a system can be realized. OBJECTIVE: To solve the problems of (1) facial nerve segmentation and (2) calculating a safety zone around the facial nerve in relation to drill-tip tracking inaccuracies. METHODS: We developed a new algorithm called NerveClick for semiautomatic segmentation of the intratemporal facial nerve centerline from temporal bone computed tomography images. We evaluated NerveClicks accuracy in an experimental setting of neuro-otologic and neurosurgical patients. Three neurosurgeons used it to segment 126 facial nerves, which were compared with the gold standard: manually segmented facial nerve centerlines. The centerlines are used as a central axis around which a tubular safety zone is built. The zones thickness incorporates the drill tip tracking errors. The system will warn when the tracked tip crosses the safety zone. RESULTS: Neurosurgeons using NerveClick could segment facial nerve centerlines with a maximum error of 0.44 ± 0.23 mm (mean ± standard deviation) on average compared with manual segmentations. CONCLUSION: Neurosurgeons using our new NerveClick algorithm can robustly segment facial nerve centerlines to construct a facial nerve safety zone, which potentially allows timely audiovisual warnings during navigated temporal bone drilling despite tracking inaccuracies.

Intra-temporal facial nerve centerline segmentation for navigated temporal bone surgery

Approaches through the temporal bone require surgeons to drill away bone to expose a target skull base lesion while evading vital structures contained within it, such as the sigmoid sinus, jugular bulb, and facial nerve. We hypothesize that an augmented neuronavigation system that continuously calculates the distance to these structures and warns if the surgeon drills too close, will aid in making safe surgical approaches. Contemporary image guidance systems are lacking an automated method to segment the inhomogeneous and complexly curved facial nerve. Therefore, we developed a segmentation method to delineate the intra-temporal facial nerve centerline from clinically available temporal bone CT images semi-automatically. Our method requires the user to provide the start- and end-point of the facial nerve in a patients CT scan, after which it iteratively matches an active appearance model based on the shape and texture of forty facial nerves. Its performance was evaluated on 20 patients by comparison to our gold standard: manually segmented facial nerve centerlines. Our segmentation method delineates facial nerve centerlines with a maximum error along its whole trajectory of 0.40±0.20 mm (mean±standard deviation). These results demonstrate that our model-based segmentation method can robustly segment facial nerve centerlines. Next, we can investigate whether integration of this automated facial nerve delineation with a distance calculating neuronavigation interface results in a system that can adequately warn surgeons during temporal bone drilling, and effectively diminishes risks of iatrogenic facial nerve palsy.

Surgical Instrument Tracking Optimizes Trans-Sphenoidal Endoscopic Treatment of Petrous Apex Cholesterol Granuloma

During endoscopic trans-sphenoidal treatment of petrous apex cholesterol granuloma, the challenge for the surgeon is to drill the posterior wall of the sphenoid sinus to reach the lesion while attempting to avoid the internal carotid artery (ICA). A refined neuronavigation technique is presented that diminishes bonework needed for exposure and marsupialization, and simultaneously minimizes risks of accidental harm to the ICA. The technique utilizes real-time intraoperative instrument tracking of a drill, enabling safe creation of a direct canal toward the cyst just medial to the paraclival ICA and of a curette for entirely image-guided marsupialization of the cysts deep areas through the canal.