Comparing spatial distributions of ALA-PpIX and indocyanine green in a whole pig brain glioma model using 3D fluorescence cryotomography.

Significance: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain. Aim: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography. Approach: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics. Results: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively). Conclusions: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.

Porcine-human glioma xenograft model. Immunosuppression and model reproducibility.

BACKGROUND: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. METHODS: Immunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. RESULTS: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. CONCLUSION: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.

Model-based image updating in deep brain stimulation with assimilation of deep brain sparse data.

BACKGROUND: Accuracy of electrode placement for deep brain stimulation (DBS) is critical to achieving desired surgical outcomes and impacts the efficacy of treating neurodegenerative diseases. Intraoperative brain shift degrades the accuracy of surgical navigation based on preoperative images. PURPOSE: We extended a model-based image updating scheme to address intraoperative brain shift in DBS surgery and improved its accuracy in deep brain. METHODS: We evaluated 10 patients, retrospectively, who underwent bilateral DBS surgery and classified them into groups of large and small deformation based on a 2 mm subsurface movement threshold and brain shift index of 5%. In each case, sparse brain deformation data were used to estimate whole brain displacements and deform preoperative CT (preCT) to generate updated CT (uCT). Accuracy of uCT was assessed using target registration errors (TREs) at the Anterior Commissure (AC), Posterior Commissure (PC), and four calcification points in the sub-ventricular area by comparing their locations in uCT with their ground truth counterparts in postoperative CT (postCT). RESULTS: In the large deformation group, TREs were reduced from 2.5 mm in preCT to 1.2 mm in uCT (53% compensation); in the small deformation group, errors were reduced from 1.25 to 0.74 mm (41%). Average reduction of TREs at AC, PC and pineal gland were significant, statistically (p ⩽ 0.01). CONCLUSIONS: With more rigorous validation of model results, this study confirms the feasibility of improving the accuracy of model-based image updating in compensating for intraoperative brain shift during DBS procedures by assimilating deep brain sparse data.

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.

Insights into the mechanisms of aqueous Cd(II) reduction and adsorption by nanoscale zerovalent iron under different atmosphere conditions.

Nanoscale zero-valent iron (NZVI) can effectively remove and recover Cd(II) from aqueous solutions. However, the oxygen effects on Cd(II) removal by NZVI have been overlooked and not well studied. In this research, the Cd MNN auger lines obtained by X-ray photoelectron spectroscopy (XPS) revealed that Cd(II) adsorbed on the NZVI surface could be reduced to Cd(0) by the Fe(0) core under anaerobic conditions. With coexisting oxygen, the Cd(II) removal efficiency declined significantly, and Cd(II) reduction was inhibited by the thickened surface γ-FeOOH layer. Furthermore, the post-oxygen intrusion corroded the generated Cd(0) and led to the dramatic leaching of Cd(II) ions. According to the density functional theory (DFT) simulation, the adsorbed Cd(II) was preferably coordinated via a monodentate model on the surface of Fe3O4 and γ-FeOOH, which are the dominant surface species of NZVI under anaerobic and aerobic conditions, respectively. Thus, γ-FeOOH with doubly coordinated hydroxyl groups provided fewer adsorption sites than Fe3O4 for Cd(II) ions. Overall, the atmospheric conditions of subsurface remediation and wastewater treatment should be considered when applying NZVI for Cd(II) removal. Favorable atmospheric conditions would improve the efficiency and cost-effectiveness of NZVI-based technologies for the practical remediation of Cd(II) pollution.

Cannabidiol Inhibits Inflammation Induced by Cutibacterium acnes-Derived Extracellular Vesicles via Activation of CB2 Receptor in Keratinocytes.

Background: Acne is a common inflammatory skin disease, while cannabidiol (CBD) is a representative non-psychoactive phytocannabinoid which has been proved to exert universal anti-inflammatory properties. This study aimed to explore the effect of CBD on acne inflammation induced by Cutibacterium acnes-derived extracellular vesicles (CEVs) in keratinocytes and reveal the underlying mechanisms. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated by CEVs in the presence of CBD or vehicle. Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels were examined by RT-PCR and ELISA. The expression of cannabinoid type-2 (CB2) receptor and transient receptor potential vanilloid type-1 (TRPV1) was detected by Western blotting. TNF-α levels in the presence of CB2 receptor antagonist (AM630) or TRPV1 antagonist (Capsazepine) were detected by RT-PCR. The activation of MAPK and NF-κB signaling pathways and the nuclear translocation of NF-κB p65 upon CBD treatment were analyzed by Western blotting and immunofluorescence assay, respectively. Results: The expression of inflammatory cytokines (IL-6, IL-8 and TNF-α) in CEVs-stimulated NHEKs was suppressed by CBD. CB2 receptor expression was upregulated by CBD, whereas CEVs-promoted TRPV1 expression was downregulated by CBD. AM630 reversed TNF-α levels inhibited by CBD. Capsazepine exerted an inhibitory effect on CEVs-induced inflammation and had synergistic effect with CBD. The phosphorylation of ERK1/2 and NF-κB p65 and nuclear translocation of NF-κB p65 were induced by CEVs but reduced by CBD. Conclusion: The results indicated that CBD could inhibit inflammation induced by CEVs in NHEKs, which was mediated by activation of CB2 receptor and enhanced by the TRPV1 antagonist, through inactivation of the MAPK and NF-κB signaling pathways. CBD might be a potential novel strategy for acne treatment in the future.

Comparative Proteomic Analysis of Membrane Vesicles from Clinical C. acnes Isolates with Differential Antibiotic Resistance.

Purpose: Cutibacterium acnes (C. acnes) is closely associated with the pathogenesis of acne, and antibiotics targeting C. acnes have been widely used for decades. However, antibiotic resistance has been increasing rapidly. Membrane vesicles (MVs) have been found to play important roles in antibiotic resistance in some bacteria. We aimed to explore the mechanism of antibiotic resistance and the virulence components within C. acnes-derived MVs. Materials and Methods: We isolated clinical C. acnes strains from the lesions of acne patients who were sensitive or resistant to the antibiotics erythromycin and clindamycin. We analyzed the proteome of MVs from four sensitive C. acnes isolates and three resistant isolates by LC-MS/MS. Results: We identified 543 proteins within the MVs of clinical C. acnes strains. Several lipases, NlpC/P60, CAMP factor, and Hta domain protein were detected as virulence factors in the C. acnes-derived MVs. The levels of two lipases and FtsZ were significantly higher in resistant C. acnes-derived MVs compared with sensitive strains (p < 0.05). Conclusion: According to the implications of this study, improper antibiotic use might not only increase antibiotic resistance in C. acnes but could also further alter the cutaneous lipid composition and aggravate host inflammation, thus resulting in worse clinical manifestations in acne patients. This study re-emphasizes that the improper use of antibiotics should be treated more seriously in clinical practice. Furthermore, to combat multidrug resistance in C. acnes, this study suggests that FtsZ inhibitors could be useful.

Accuracy of Stereovision-Updated Versus Preoperative CT-Based Image Guidance in Multilevel Lumbar Pedicle Screw Placement: A Cadaveric Swine Study.

Change in vertebral position between preoperative imaging and the surgical procedure reduces the accuracy of image-guided spinal surgery, requiring repeated imaging and surgical field registration, a process that takes time and exposes patients to additional radiation. We developed a handheld, camera-based, deformable registration system (intraoperative stereovision, iSV) to register the surgical field automatically and compensate for spinal motion during surgery without further radiation exposure. Methods: We measured motion-induced errors in image-guided lumbar pedicle screw placement in 6 whole-pig cadavers using state-of-the-art commercial spine navigation (StealthStation; Medtronic) and iSV registration that compensates for intraoperative vertebral motion. We induced spinal motion by using preoperative computed tomography (pCT) of the lumbar spine performed in the supine position with accentuated lordosis and performing surgery with the animal in the prone position. StealthStation registration of pCT occurred using metallic fiducial markers implanted in each vertebra, and iSV data were acquired to perform a deformable registration between pCT and the surgical field. Sixty-eight pedicle screws were placed in 6 whole-pig cadavers using iSV and StealthStation registrations in random order of vertebral level, relying only on image guidance without invoking the surgeon's judgment. The position of each pedicle screw was assessed with post-procedure CT and confirmed via anatomical dissection. Registration errors were assessed on the basis of implanted fiducials. Results: The frequency and severity of pedicle screw perforation were lower for iSV registration compared with StealthStation (97% versus 68% with Grade 0 medial perforation for iSV and StealthStation, respectively). Severe perforation occurred only with StealthStation (18% versus 0% for iSV). The overall time required for iSV registration (computational efficiency) was ∼10 to 15 minutes and was comparable with StealthStation registration (∼10 min). The mean target registration error was smaller for iSV relative to StealthStation (2.81 ± 0.91 versus 8.37 ± 1.76 mm). Conclusions: Pedicle screw placement was more accurate with iSV registration compared with state-of-the-art commercial navigation based on preoperative CT when alignment of the spine changed during surgery. Clinical Relevance: The iSV system compensated for intervertebral motion, which obviated the need for repeated vertebral registration while providing efficient, accurate, radiation-free navigation during open spinal surgery.

A level-wise spine registration framework to account for large pose changes.

PURPOSES: Accurate and efficient spine registration is crucial to success of spine image guidance. However, changes in spine pose cause intervertebral motion that can lead to significant registration errors. In this study, we develop a geometrical rectification technique via nonlinear principal component analysis (NLPCA) to achieve level-wise vertebral registration that is robust to large changes in spine pose. METHODS: We used explanted porcine spines and live pigs to develop and test our technique. Each sample was scanned with preoperative CT (pCT) in an initial pose and rescanned with intraoperative stereovision (iSV) in a different surgical posture. Patient registration rectified arbitrary spinal postures in pCT and iSV into a common, neutral pose through a parameterized moving-frame approach. Topologically encoded depth projection 2D images were then generated to establish invertible point-to-pixel correspondences. Level-wise point correspondences between pCT and iSV vertebral surfaces were generated via 2D image registration. Finally, closed-form vertebral level-wise rigid registration was obtained by directly mapping 3D surface point pairs. Implanted mini-screws were used as fiducial markers to measure registration accuracy. RESULTS: In seven explanted porcine spines and two live animal surgeries (maximum in-spine pose change of 87.5 mm and 32.7 degrees averaged from all spines), average target registration errors (TRE) of 1.70 ± 0.15 mm and 1.85 ± 0.16 mm were achieved, respectively. The automated spine rectification took 3-5 min, followed by an additional 30 secs for depth image projection and level-wise registration. CONCLUSIONS: Accuracy and efficiency of the proposed level-wise spine registration support its application in human open spine surgeries. The registration framework, itself, may also be applicable to other intraoperative imaging modalities such as ultrasound and MRI, which may expand utility of the approach in spine registration in general.

Hand-Held Stereovision System for Image Updating in Open Spine Surgery.

BACKGROUND: Image guidance in open spinal surgery is compromised by changes in spinal alignment between preoperative images and surgical positioning. We evaluated registration of stereo-views of the surgical field to compensate for vertebral alignment changes. OBJECTIVE: To assess accuracy and efficiency of an optically tracked hand-held stereovision (HHS) system to acquire images of the exposed spine during surgery. METHODS: Standard midline posterior approach exposed L1 to L6 in 6 cadaver porcine spines. Fiducial markers were placed on each vertebra as "ground truth" locations. Spines were positioned supine with accentuated lordosis, and preoperative computed tomography (pCT) was acquired. Spines were re-positioned in a neutral prone posture, and locations of fiducials were acquired with a tracked stylus. Intraoperative stereovision (iSV) images were acquired and 3-dimensional (3D) surfaces of the exposed spine were reconstructed. HHS accuracy was assessed in terms of distances between reconstructed fiducial marker locations and their tracked counterparts. Level-wise registrations aligned pCT with iSV to account for changes in spine posture. Accuracy of updated computed tomography (uCT) was assessed using fiducial markers and other landmarks. RESULTS: Acquisition time for each image pair was <1 s. Mean reconstruction time was <1 s for each image pair using batch processing, and mean accuracy was 1.2 ± 0.6 mm across 6 cases. Mean errors of uCT were 3.1 ± 0.7 and 2.0 ± 0.5 mm on the dorsal and ventral sides, respectively. CONCLUSION: Results suggest that a portable HHS system offers potential to acquire accurate image data from the surgical field to facilitate surgical navigation during open spine surgery.

Model-Based Image Updating for Brain Shift in Deep Brain Stimulation Electrode Placement Surgery.

OBJECTIVE: The efficacy of deep brain stimulation (DBS) depends on accurate placement of electrodes. Although stereotactic frames enable co-registration of image-based surgical planning and the operative field, the accuracy of electrode placement can be degraded by intra-operative brain shift. In this study, we adapted a biomechanical model to estimate whole brain displacements from which we deformed preoperative CT (preCT) to generate an updated CT (uCT) that compensates for brain shift. METHODS: We drove the deformation model using displacement data derived from deformation in the frontal cortical surface that occurred during the DBS intervention. We evaluated 15 patients, retrospectively, who underwent bilateral DBS surgery, and assessed the accuracy of uCT in terms of target registration error (TRE) relative to a CT acquired post-placement (postCT). We further divided subjects into large (Group L) and small (Group S) deformation groups based on a TRE threshold of 1.6mm. Anterior commissure (AC), posterior commissure (PC) and pineal gland (PG) were identified on preCT and postCT and used to quantify TREs in preCT and uCT. RESULTS: In the group of large brain deformation, average TREs for uCT were 1.11 ± 0.13 and 1.07 ± 0.38 mm at AC and PC, respectively, compared to 1.85 ± 0.17 and 0.92 ± 0.52 mm for preCT. The model updating approach improved AC localization but did not alter TREs at PC. CONCLUSION: This preliminary study suggests that our image updating method may compensate for brain shift around surgical targets of importance during DBS surgery, although further investigation is warranted before conclusive evidence will be available. SIGNIFICANCE: With further development and evaluation, our model-based image updating method using intraoperative sparse data may compensate for brain shift in DBS surgery efficiently, and have utility in updating targeting coordinates.

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.

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.

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.

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).

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.

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.

Intraoperative image updating for brain shift following dural opening.

OBJECTIVE Preoperative magnetic resonance images (pMR) are typically coregistered to provide intraoperative navigation, the accuracy of which can be significantly compromised by brain deformation. In this study, the authors generated updated MR images (uMR) in the operating room (OR) to compensate for brain shift due to dural opening, and evaluated the accuracy and computational efficiency of the process. METHODS In 20 open cranial neurosurgical cases, a pair of intraoperative stereovision (iSV) images was acquired after dural opening to reconstruct a 3D profile of the exposed cortical surface. The iSV surface was registered with pMR to detect cortical displacements that were assimilated by a biomechanical model to estimate whole-brain nonrigid deformation and produce uMR in the OR. The uMR views were displayed on a commercial navigation system and compared side by side with the corresponding coregistered pMR. A tracked stylus was used to acquire coordinate locations of features on the cortical surface that served as independent positions for calculating target registration errors (TREs) for the coregistered uMR and pMR image volumes. RESULTS The uMR views were visually more accurate and well aligned with the iSV surface in terms of both geometry and texture compared with pMR where misalignment was evident. The average misfit between model estimates and measured displacements was 1.80 ± 0.35 mm, compared with the average initial misfit of 7.10 ± 2.78 mm between iSV and pMR, and the average TRE was 1.60 ± 0.43 mm across the 20 patients in the uMR image volume, compared with 7.31 ± 2.82 mm on average in the pMR cases. The iSV also proved to be accurate with an average error of 1.20 ± 0.37 mm. The overall computational time required to generate the uMR views was 7-8 minutes. CONCLUSIONS This study compensated for brain deformation caused by intraoperative dural opening using computational model-based assimilation of iSV cortical surface displacements. The uMR proved to be more accurate in terms of model-data misfit and TRE in the 20 patient cases evaluated relative to pMR. The computational time was acceptable (7-8 minutes) and the process caused minimal interruption of surgical workflow.

Intraoperative fiducial-less patient registration using volumetric 3D ultrasound: a prospective series of 32 neurosurgical cases.

OBJECT: Fiducial-based registration (FBR) is used widely for patient registration in image-guided neurosurgery. The authors of this study have developed an automatic fiducial-less registration (FLR) technique to find the patient-to-image transformation by directly registering 3D ultrasound (3DUS) with MR images without incorporating prior information. The purpose of the study was to evaluate the performance of the FLR technique when used prospectively in the operating room and to compare it with conventional FBR. METHODS: In 32 surgical patients who underwent conventional FBR, preoperative T1-weighted MR images (pMR) with attached fiducial markers were acquired prior to surgery. After craniotomy but before dural opening, a set of 3DUS images of the brain volume was acquired. A 2-step registration process was executed immediately after image acquisition: 1) the cortical surfaces from pMR and 3DUS were segmented, and a multistart sum-of-squared-intensity-difference registration was executed to find an initial alignment between down-sampled binary pMR and 3DUS volumes; and 2) the alignment was further refined by a mutual information-based registration between full-resolution grayscale pMR and 3DUS images, and a patient-to-image transformation was subsequently extracted. RESULTS: To assess the accuracy of the FLR technique, the following were quantified: 1) the fiducial distance error (FDE); and 2) the target registration error (TRE) at anterior commissure and posterior commissure locations; these were compared with conventional FBR. The results showed that although the average FDE (6.42 ± 2.05 mm) was higher than the fiducial registration error (FRE) from FBR (3.42 ± 1.37 mm), the overall TRE of FLR (2.51 ± 0.93 mm) was lower than that of FBR (5.48 ± 1.81 mm). The results agreed with the intent of the 2 registration techniques: FBR is designed to minimize the FRE, whereas FLR is designed to optimize feature alignment and hence minimize TRE. The overall computational cost of FLR was approximately 4-5 minutes and minimal user interaction was required. CONCLUSIONS: Because the FLR method directly registers 3DUS with MR by matching internal image features, it proved to be more accurate than FBR in terms of TRE in the 32 patients evaluated in this study. The overall efficiency of FLR in terms of the time and personnel involved is also improved relative to FBR in the operating room, and the method does not require additional image scans immediately prior to surgery. The performance of FLR and these results suggest potential for broad clinical application.

Intraoperative CT as a registration benchmark for intervertebral motion compensation in image-guided open spinal surgery.

PURPOSE: An accurate and reliable benchmark of registration accuracy and intervertebral motion compensation is important for spinal image guidance. In this study, we evaluated the utility of intraoperative CT (iCT) in place of bone-implanted screws as the ground-truth registration and illustrated its use to benchmark the performance of intraoperative stereovision (iSV). METHODS: A template-based, multi-body registration scheme was developed to individually segment and pair corresponding vertebrae between preoperative CT and iCT of the spine. Intervertebral motion was determined from the resulting vertebral pair-wise registrations. The accuracy of the image-driven registration was evaluated using surface-to-surface distance error (SDE) based on segmented bony features and was independently verified using point-to-point target registration error (TRE) computed from bone-implanted mini-screws. Both SDE and TRE were used to assess the compensation accuracy using iSV. RESULTS: The iCT-based technique was evaluated on four explanted porcine spines (20 vertebral pairs) with artificially induced motion. We report a registration accuracy of 0.57 [Formula: see text] 0.32 mm (range 0.34-1.14 mm) and 0.29 [Formula: see text] 0.15 mm (range 0.14-0.78 mm) in SDE and TRE, respectively, for all vertebrae pooled, with an average intervertebral rotation of [Formula: see text] (range 1.5[Formula: see text]-7.9[Formula: see text]). The iSV-based compensation accuracy for one sample (four vertebrae) was 1.32 [Formula: see text] 0.19 mm and 1.72 [Formula: see text] 0.55 mm in SDE and TRE, respectively, exceeding the recommended accuracy of 2 mm. CONCLUSION: This study demonstrates the effectiveness of iCT in place of invasive fiducials as a registration ground truth. These findings are important for future development of on-demand spinal image guidance using radiation-free images such as stereovision and ultrasound on human subjects.