A birefringent spectral demultiplexer enables fast hyper-spectral imaging of protoporphyrin IX during neurosurgery.

Hyperspectral imaging and spectral analysis quantifies fluorophore concentration during fluorescence-guided surgery1-6. However, acquisition of the multiple wavelengths required to implement these methods can be time-consuming and hinder surgical workflow. To this end, a snapshot hyperspectral imaging system capable of acquiring 64 channels of spectral data simultaneously was developed for rapid hyperspectral imaging during neurosurgery. The system uses a birefringent spectral demultiplexer to split incoming light and redirect wavelengths to different sections of a large format microscope sensor. Its configuration achieves high optical throughput, accepts unpolarized input light and exceeds channel count of prior image-replicating imaging spectrometers by 4-fold. Tissue-simulating phantoms consisting of serial dilutions of the fluorescent agent characterize system linearity and sensitivity, and comparisons to performance of a liquid crystal tunable filter based hyperspectral imaging device are favorable. The new instrument showed comparable, if not improved, sensitivity at low fluorophore concentrations; yet, acquired wide-field images at more than 70-fold increase in frame rate. Image data acquired in the operating room during human brain tumor resection confirm these findings. The new device is an important advance in achieving real-time quantitative imaging of fluorophore concentration for guiding surgery.

Improving the Usability of 5-Aminolevulinic Acid Fluorescence-Guided Surgery by Adding an Optimized Secondary Light Source.

BACKGROUND: Tumors that take up and metabolize 5-aminolevulinic acid emit bright pink fluorescence when illuminated with blue light, aiding surgeons in identifying the margin of resection. The adoption of this method is hindered by the blue light illumination, which is too dim to safely operate under and therefore necessitates switching back and forth from white-light mode. The aim of this study was to examine the addition of an optimized secondary illuminant adapter to improve usability of blue-light mode without degrading tumor contrast. METHODS: Color science methods were used to evaluate the color of the secondary illuminant and its impact on color rendering index as well as the tumor-to-background color contrast in data collected from 7 patients with high-grade gliomas (World Health Organization grade III and IV). A secondary illuminant adapter was built to provide 475-600 nm light the intensity of which can be controlled by the surgeon and was evaluated in 2 additional patients. RESULTS: Secondary illuminant color had opposing effects on color rendering index and tumor-to-background color contrast; providing surgeon control of intensity allows this trade-off to be balanced in real time. Demonstration in 2 high-grade glioma cases confirms this, showing that additional visibility adds value when intensity can be controlled by the surgeon. CONCLUSIONS: Addition of a secondary illuminant may mitigate surgeon complaints that the operative field is too dark under the blue light illumination required for 5-aminolevulinic acid fluorescence guidance by providing improved color rendering index without completely sacrificing tumor-to-background color contrast.

Quantification of Subdural Electrode Shift Between Initial Implantation, Postimplantation Computed Tomography, and Subsequent Resection Surgery.

BACKGROUND: Subdural electrodes are often implanted for localization of epileptic regions. Postoperative computed tomography (CT) is typically acquired to locate electrode positions for planning any subsequent surgical resection. Electrodes are assumed to remain stationary between CT acquisition and resection surgery. OBJECTIVE: To quantify subdural electrode shift that occurred between the times of implantation (Crani 1), postoperative CT acquisition, and resection surgery (Crani 2). METHODS: Twenty-three patients in this case series undergoing subdural electrode implantation were evaluated. Preoperative magnetic resonance and postoperative CT were acquired and coregistered, and electrode positions were extracted from CT. Intraoperative positions of electrodes and the cortical surface were digitized with a coregistered stereovision system. Movement of the exposed cortical surface was also tracked, and change in electrode positions was calculated relative to both the skull and the cortical surface. RESULTS: In the 23 cases, average shift of electrode positions was 8.0 ± 3.3 mm between Crani 1 and CT, 9.2 ± 3.7 mm between CT and Crani 2, and 6.2 ± 3.0 mm between Crani 1 and Crani 2. The average cortical shift was 4.7 ± 1.4 mm with 2.9 ± 1.0 mm in the lateral direction. The average shift of electrode positions relative to the cortical surface between Crani 1 and Crani 2 was 5.5 ± 3.7 mm. CONCLUSION: The results show that electrodes shifted laterally not only relative to the skull, but also relative to the cortical surface, thereby displacing the electrodes from their initial placement on the cortex. This has significant clinical implications for resection based upon seizure activity and functional mapping derived from intracranial electrodes.

5-Aminolevulinic Acid-Induced Fluorescence in Focal Cortical Dysplasia: Report of 3 Cases.

BACKGROUND: Three patients enrolled in a clinical trial of 5-aminolevulinic-acid (5-ALA)-induced fluorescence-guidance, which has been demonstrated to facilitate intracranial tumor resection, were found on neuropathological examination to have focal cortical dysplasia (FCD). OBJECTIVE: To evaluate in this case series visible fluorescence and quantitative levels of protoporphyrin IX (PpIX) during surgery and correlate these findings with preoperative magnetic resonance imaging (MRI) and histopathology. METHODS: Patients were administered 5-ALA (20 mg/kg) approximately 3 h prior to surgery and underwent image-guided, microsurgical resection of their MRI- and electrophysiologically identified lesions. Intraoperative visible fluorescence was evaluated using an operating microscope adapted with a commercially available blue light module. Quantitative PpIX levels were assessed using a handheld fiber-optic probe and a wide-field imaging spectrometer. Sites of fluorescence measurements were co-registered with both preoperative MRI and histopathological analysis. RESULTS: Three patients with a pathologically confirmed diagnosis of FCD (Types 1b, 2a, and 2b) underwent surgery. All patients demonstrated some degree of visible fluorescence (faint or moderate), and all patients had quantitatively elevated concentrations of PpIX. No evidence of neoplasia was identified on histopathology, and in 1 patient, the highest concentrations of PpIX were found at a tissue site with marked gliosis but no typical histological features of FCD. CONCLUSION: FCD has been found to be associated with intraoperative 5-ALA-induced visible fluorescence and quantitatively confirmed elevated concentrations of the fluorophore PpIX in 3 patients. This finding suggests that there may be a role for fluorescence-guidance during surgical intervention for epilepsy-associated FCD.

Image Updating for Brain Shift Compensation During Resection.

BACKGROUND: In open-cranial neurosurgery, preoperative magnetic resonance (pMR) images are typically coregistered for intraoperative guidance. Their accuracy can be significantly degraded by intraoperative brain deformation, especially when resection is involved. OBJECTIVE: To produce model updated MR (uMR) images to compensate for brain shift that occurred during resection, and evaluate the performance of the image-updating process in terms of accuracy and computational efficiency. METHODS: In 14 resection cases, intraoperative stereovision image pairs were acquired after dural opening and during resection to generate displacement maps of the surgical field. These data were assimilated by a biomechanical model to create uMR volumes of the evolving surgical field. A tracked stylus provided independent measurements of feature locations to quantify target registration errors (TREs) in the original coregistered pMR and uMR as surgery progressed. RESULTS: Updated MR TREs were 1.66 ± 0.27 and 1.92 ± 0.49 mm in the 14 cases after dural opening and after partial resection, respectively, compared to 8.48 ± 3.74 and 8.77 ± 4.61 mm for pMR, respectively. The overall computational time for generating uMRs after partial resection was less than 10 min. CONCLUSION: We have developed an image-updating system to compensate for brain deformation during resection using a computational model with data assimilation of displacements measured with intraoperative stereovision imaging that maintains TREs less than 2 mm on average.

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.

OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis. RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery. CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional blue-light excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov).

Stereovision Co-Registration in Image-Guided Spinal Surgery: Accuracy Assessment Using Explanted Porcine Spines.

BACKGROUND: Current methods of spine registration for image guidance have a variety of limitations related to accuracy, efficiency, and cost. OBJECTIVE: To define the accuracy of stereovision-mediated co-registration of a spinal surgical field. METHODS: A total of 10 explanted porcine spines were used. Dorsal soft tissue was removed to a variable degree. Bone screw fiducials were placed in each spine and high-resolution computed tomography (CT) scanning performed. Stereoscopic images were then obtained using a tracked, calibrated stereoscopic camera system; images were processed, reconstructed, and segmented in a semi-automated manner. A multistart registration of the reconstructed spinal surface with preoperative CT was performed. Target registration error (TRE) in the region of the laminae and facets was then determined, using bone screw fiducials not included in the original registration process. Each spine also underwent multilevel laminectomy, and TRE was then recalculated for varying amounts of bone removal. RESULTS: The mean TRE of stereovision registration was 2.19 ± 0.69 mm when all soft tissue was removed and 2.49 ± 0.74 mm when limited soft tissue removal was performed. Accuracy of the registration process was not adversely affected by laminectomy. CONCLUSION: Stereovision offers a promising means of registering an open, dorsal spinal surgical field. In this study, overall mean accuracy of the registration was 2.21 mm, even when bony anatomy was partially obscured by soft tissue or when partial midline laminectomy had been performed.

Use of Stereovision for Intraoperative Coregistration of a Spinal Surgical Field: A Human Feasibility Study.

BACKGROUND: The use of image guidance during spinal surgery has been limited by several anatomic factors such as intervertebral segment motion and ineffective spine immobilization. In its current form, the surgical field is coregistered with a preoperative computed tomography (CT), often obtained in a different spinal confirmation, or with intraoperative cross-sectional imaging. Stereovision offers an alternative method of registration. OBJECTIVE: To demonstrate the feasibility of stereovision-mediated coregistration of a human spinal surgical field using a proof-of-principle study, and to provide preliminary assessments of the technique's accuracy. METHODS: A total of 9 subjects undergoing image-guided pedicle screw placement also underwent stereovision-mediated coregistration with preoperative CT imaging. Stereoscopic images were acquired using a tracked, calibrated stereoscopic camera system mounted on an operating microscope. Images were processed, reconstructed, and segmented in a semi-automated manner. A multistart registration of the reconstructed spinal surface with preoperative CT was performed. Registration accuracy, measured as surface-to-surface distance error, was compared between stereovision registration and a standard registration. RESULTS: The mean surface reconstruction error of the stereovision-acquired surface was 2.20 ± 0.89 mm. Intraoperative coregistration with stereovision was performed with a mean error of 1.48 ± 0.35 mm compared to 2.03 ± 0.28 mm using a standard point-based registration method. The average computational time for registration with stereovision was 95 ± 46 s (range 33-184 s) vs 10to 20 min for standard point-based registration. CONCLUSION: Semi-automated registration of a spinal surgical field using stereovision is possible with accuracy that is at least comparable to current landmark-based techniques.

Review of fluorescence guided surgery visualization and overlay techniques.

In fluorescence guided surgery, data visualization represents a critical step between signal capture and display needed for clinical decisions informed by that signal. The diversity of methods for displaying surgical images are reviewed, and a particular focus is placed on electronically detected and visualized signals, as required for near-infrared or low concentration tracers. Factors driving the choices such as human perception, the need for rapid decision making in a surgical environment, and biases induced by display choices are outlined. Five practical suggestions are outlined for optimal display orientation, color map, transparency/alpha function, dynamic range compression, and color perception check.