Kelvin Mok

Intraoperative brain cancer detection with Raman spectroscopy in humans

A handheld Raman spectroscopy probe enabled detection of invasive brain cancer intraoperatively in patients with grade 2 to 4 gliomas. Probing for brain tumors Gliomas are invasive cancers, spreading quietly throughout the brain. They pose a formidable challenge to surgeons who try to remove all cancer cells during resection; leaving any cancer behind can lower the patient’s prospects for survival. Jermyn et al. adapted Raman spectroscopy for the operating room by developing an imaging technique that uses a commercially available, handheld contact fiber optic probe. The probe’s optic cables were connected to a near-infrared laser, for stimulating tissue molecules; in turn, these components were linked to a computer to visualize resulting spectra in real time. When held against human brain tissue, the probe measured the Raman scattering signal, which was separated from background signals and differentiated from “normal” tissues using certain algorithms. The authors tested the probe in 17 patients with grade 2 to 4 gliomas who were undergoing surgery and compared imaging results with 161 biopsy samples. Intraoperative Raman imaging allowed the authors to detect both invasive and dense cancer cells with an accuracy of 92%. By comparison, the surgeon, using standard surgical tools like the bright-field microscope and magnetic resonance imaging, identified cancer with 73% accuracy. Such label-free, portable, intraoperative imaging technologies will be important in improving the efficiency of tumor resections and, in turn, for extending survival times of glioma patients. Cancers are often impossible to visually distinguish from normal tissue. This is critical for brain cancer where residual invasive cancer cells frequently remain after surgery, leading to disease recurrence and a negative impact on overall survival. No preoperative or intraoperative technology exists to identify all cancer cells that have invaded normal brain. To address this problem, we developed a handheld contact Raman spectroscopy probe technique for live, local detection of cancer cells in the human brain. Using this probe intraoperatively, we were able to accurately differentiate normal brain from dense cancer and normal brain invaded by cancer cells, with a sensitivity of 93% and a specificity of 91%. This Raman-based probe enabled detection of the previously undetectable diffusely invasive brain cancer cells at cellular resolution in patients with grade 2 to 4 gliomas. This intraoperative technology may therefore be able to classify cell populations in real time, making it an ideal guide for surgical resection and decision-making.

Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals.

We examined the effects of learning a second language (L2) on brain structure. Cortical thickness was measured in the MRI datasets of 22 monolinguals and 66 bilinguals. Some bilingual subjects had learned both languages simultaneously (0-3 years) while some had learned their L2 after achieving proficiency in their first language during either early (4-7 years) or late childhood (8-13 years). Later acquisition of L2 was associated with significantly thicker cortex in the left inferior frontal gyrus (IFG) and thinner cortex in the right IFG. These effects were seen in the group comparisons of monolinguals, simultaneous bilinguals and early and late bilinguals. Within the bilingual group, significant correlations between age of acquisition of L2 and cortical thickness were seen in the same regions: cortical thickness correlated with age of acquisition positively in the left IFG and negatively in the right IFG. Interestingly, the monolinguals and simultaneous bilinguals did not differ in cortical thickness in any region. Our results show that learning a second language after gaining proficiency in the first language modifies brain structure in an age-dependent manner whereas simultaneous acquisition of two languages has no additional effect on brain development.

Characterization of a Raman spectroscopy probe system for intraoperative brain tissue classification

A detailed characterization study is presented of a Raman spectroscopy system designed to maximize the volume of resected cancer tissue in glioma surgery based on in vivo molecular tissue characterization. It consists of a hand-held probe system measuring spectrally resolved inelastically scattered light interacting with tissue, designed and optimized for in vivo measurements. Factors such as linearity of the signal with integration time and laser power, and their impact on signal to noise ratio, are studied leading to optimal data acquisition parameters. The impact of ambient light sources in the operating room is assessed and recommendations made for optimal operating conditions. In vivo Raman spectra of normal brain, cancer and necrotic tissue were measured in 10 patients, demonstrating that real-time inelastic scattering measurements can distinguish necrosis from vital tissue (including tumor and normal brain tissue) with an accuracy of 87%, a sensitivity of 84% and a specificity of 89%.

Tractography of the amygdala and hippocampus: anatomical study and application to selective amygdalohippocampectomy.

OBJECT The aim of this study was to evaluate, using diffusion tensor tractography, the white matter fibers crossing the hippocampus and the amygdala, and to perform a volumetric analysis and an anatomical study of the connections of these 2 structures. As a second step, the authors studied the white matter tracts crossing a virtual volume of resection corresponding to a selective amygdalohippocampectomy. METHODS Twenty healthy right-handed individuals underwent 3-T MR imaging. Volumetric regions of interest were manually created to delineate the amygdala, the hippocampus, and the volume of resection. White matter fiber tracts were parcellated using the fiber assignment for continuous tracking tractography algorithm. All fibers were registered with the anatomical volumes. RESULTS In all participants, the authors identified fibers following the hippocampus toward the fornix, the splenium of the corpus callosum, and the dorsal hippocampal commissure. With respect to the fibers crossing the amygdala, the authors identified the stria terminalis and the uncinate fasciculus. The virtual resection disrupted part of the fornix, fibers connecting the 2 hippocampi, and fibers joining the orbitofrontal cortex. The approach created a theoretical frontotemporal disconnection and also interrupted fibers joining the temporal pole and the occipital area. CONCLUSIONS This diffusion tensor tractography study allowed for good visualization of some of the connections of the amygdala and hippocampus. The authors observed that the virtual selective amygdalohippocampectomy disconnected a large number of fibers connecting frontal, temporal, and occipital areas.

Automatic trajectory planning of DBS neurosurgery from multi-modal MRI datasets

We propose an automated method for preoperative trajectory planning of deep brain stimulation image-guided neurosurgery. Our framework integrates multi-modal MRI analysis (T1w, SWI, TOF-MRA) to determine an optimal trajectory to DBS targets (subthalamic nuclei and globus pallidus interna) while avoiding critical brain structures for prevention of hemorrhages, loss of function and other complications. Results show that our method is well suited to aggregate many surgical constraints and allows the analysis of thousands of trajectories in less than 1/10th of the time for manual planning. Finally, a qualitative evaluation of computed trajectories resulted in the identification of potential new constraints, which are not addressed in the current literature, to better mimic the decision-making of the neurosurgeon during DBS planning.

Pathologic substrates of focal epilepsy influence the generation of high-frequency oscillations.

Although a clear correlation has been observed between high‐frequency oscillations (HFOs) and the seizure‐onset zone in distinct lesions, the role of the underlying pathologic substrates in the generation of HFOs is not well established. We aimed to investigate HFO correlates of different pathologic substrates in patients with drug‐resistant epilepsy, and to examine the relation of HFOs with the anatomic location of the dysplastic lesion and surrounding tissue in patients with focal cortical dysplasia (FCD).

Augmented reality in neurovascular surgery: feasibility and first uses in the operating room

PurposeThe aim of this report is to present a prototype augmented reality (AR) intra-operative brain imaging system. We present our experience of using this new neuronavigation system in neurovascular surgery and discuss the feasibility of this technology for aneurysms, arteriovenous malformations (AVMs), and arteriovenous fistulae (AVFs).MethodsWe developed an augmented reality system that uses an external camera to capture the live view of the patient on the operating room table and to merge this view with pre-operative volume-rendered vessels. We have extensively tested the system in the laboratory and have used the system in four surgical cases: one aneurysm, two AVMs and one AVF case.ResultsThe developed AR neuronavigation system allows for precise patient-to-image registration and calibration of the camera, resulting in a well-aligned augmented reality view. Initial results suggest that augmented reality is useful for tailoring craniotomies, localizing vessels of interest, and planning resection corridors.ConclusionAugmented reality is a promising technology for neurovascular surgery. However, for more complex anomalies such as AVMs and AVFs, better visualization techniques that allow one to distinguish between arteries and veins and determine the absolute depth of a vessel of interest are needed.

Augmented Reality in Neurovascular Surgery: First Experiences

In neurovascular surgery, the surgeon must navigate among eloquent areas, through complex neurovascular anatomy to a particular vascular malformation or anomaly. Augmented reality (AR) visualization may be used to show vessels not visible when looking at the brain surface and to aid navigation by bringing into spatial alignment pre-operative vascular data with the real patient anatomy. In using AR, we may aid the surgeon in planning the craniotomy to obtain the optimal resection corridor and reduce the time to localize and identify important vessels. In the following paper, we describe the first uses of our AR neuronavigation system in the operating room (OR). Specifically, we describe the system’s use in three different neurovascular cases, an aneurysm case, an arteriovenous malfromation, and a dural arteriovenous fistula. Furthermore, we give a qualitative evaluation based on comments from the OR and post-operative discussions with the neurosurgeons.

Pedicle violation and Navigational errors in pedicle screw insertion using the intraoperative O-arm: A preliminary report

Background Use of computer-assisted insertion of pedicle screws has some advantages owing to the reportedly decreased incidence of pedicle breach and clinical events. Registration-based methods based on preoperative computed tomography imaging, 2D fluoroscopy, and 3D fluoroscopy are the most popular, however each has its limitations. O-arm–based navigation, which uses intraoperative acquisition and registration of navigated images, may overcome many of these disadvantages. We set out to study the clinical accuracy and navigational accuracy for pedicle screw insertion using our recently acquired O-arm and present our preliminary findings. Methods The first 26 patients operated consecutively for L4-5 fusion were included in the study. O-arm–based navigation was used to insert the pedicle screws. Postoperative computed tomography images were acquired and assessed for pedicle breach and anterior cortical perforation. Planned trajectories of each screw were compared with the actual trajectories in the postoperative images to assess navigational accuracy in both axial and sagittal planes. Results A total of 104 screws were inserted. One screw (1%) breached the pedicle laterally. Nonsignificant anterolateral cortical perforations were noted in 7 screws (6.7%), all of which occurred at L5 level. The mean axial and sagittal navigational error was 2.3° (±1.7) and 3.1° (±2.3), respectively. There were no significant differences in the errors between L4 or L5 level. The occurrence of anterior perforation correlated with the degree of axial (P = .02) but not sagittal (P = .12) navigational error. There were no clinical events related to the screw insertion. Conclusion Use of O-arm–guided pedicle screw insertion was associated with low incidence of pedicle breach (1%) and a low range of navigational error in both sagittal and axial planes. Anterolateral vertebral body perforation was higher at L5 without any negative clinical events. Despite the high need for technical support, we found that O-arm was a very efficient tool for accurate pedicle screw insertion.

Automatic Optimization of Depth Electrode Trajectory Planning

This paper presents a fully automatic procedure for optimization of depth electrode implantation planning in epilepsy. To record intracranial EEG in some patients with intractable epilepsy, depth electrodes are implanted through holes in the skull. The proposed fully automatic procedure maximizes recording coverage of the target volume by estimating the EEG recorded from each contact, while minimizing the risk of approaching vessels and other critical structures. All structures, including the hippocampus and amygdala were automatically segmented. We retrospectively validated the procedure for mesial temporal lobe implantations in 11 hemispheres. The automatic trajectories recorded from a larger volume of interest than the original manually selected trajectories while better avoiding the segmented structures. The procedure is integrated into a neuronavigation system enabling the surgeon to visualize the selected trajectories from an ordered list and, if necessary, enables re-planning a trajectory in near real time.