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Pramod V. Butte, Adam Mamelak, Julia Parrish-Novak, Doniel Drazin, Faris Shweikeh, Pallavi R. Gangalum, Alexandra Chesnokova, Julia Y. Ljubimova, and Keith Black

Object

The intraoperative clear delineation between brain tumor and normal tissue in real time is required to ensure near-complete resection without damaging the nearby eloquent brain. Tumor Paint BLZ-100, a tumor ligand chlorotoxin (CTX) conjugated to indocyanine green (ICG), has shown potential to be a targeted contrast agent. There are many infrared imaging systems in use, but they are not optimized to the low concentration and amount of ICG. The authors present a novel proof-of-concept near-infrared (NIR) imaging system using a standard charge-coupled device (CCD) camera for visualizing low levels of ICG attached to the tumors. This system is small, inexpensive, and sensitive. The imaging system uses a narrow-band laser at 785 nm and a notch filter in front of the sensor at the band. The camera is a 2-CCD camera, which uses identical CCDs for both visible and NIR light.

Methods

The NIR system is tested with serial dilution of BLZ-100 from 1 μM to 50 pM in 5% Intralipid solution while the excitation energy is varied from 5 to 40 mW/cm2. The analog gain of the CCD was changed from 0, 6, and 12 dB to determine the signal-to-noise ratio. In addition to the Intralipid solution, BLZ-100 was injected 48 hours before euthanizing the mice that were implanted with the human glioma cell line. The brain was removed and imaged using the NIR imaging system.

Results

The authors' results show that the NIR imaging system using a standard CCD is able to visualize the ICG down to 50 nM of concentration with a high signal-to-noise ratio. The preliminary experiment on human glioma implanted in mouse brains demonstrated that BLZ-100 has a high affinity for glioma compared with normal brain tissue. Additionally, the results show that NIR excitation is able to penetrate deeply and has a potential to visualize metastatic lesions that are separate from the main tumor.

Conclusions

The authors have seen that BLZ-100 has a very high affinity toward human gliomas. They also describe a small, cost-effective, and sensitive NIR system for visualizing brain tumors tagged using BLZ-100. The authors hope that the use of BLZ-100 along with NIR imaging will be useful to delineate the brain tumors in real time and assist surgeons in near-complete tumor removal to increase survival and reduce neurological deficits.

Restricted access

Christopher R. Pasarikovski, Jerry C. Ku, Julia Keith, Joel Ramjist, Yuta Dobashi, Stefano M. Priola, Leodante da Costa, Ashish Kumar, and Victor X. D. Yang

OBJECTIVE

Although the majority of patients with cerebral venous sinus thrombosis (CVST) will improve with anticoagulation therapy, a portion of patients will either present in a comatose state or continue to deteriorate clinically despite early anticoagulation. In these cases, along with treating the underlying thrombophilia, timely thrombolysis may be beneficial. Repurposed arterial thrombectomy devices may not perform as expected in the cerebral venous sinus, and there are currently no preclinical endovascular thrombectomy (EVT) models for CVST. Contrary to arterial stroke research, preclinical models utilized to test various endovascular techniques and devices are lacking. The purpose of this research was to develop a reliable preclinical animal model for the testing of endovascular strategies to treat CVST.

METHODS

Five consecutive male Yorkshire swine weighing 45 kg were utilized. Thrombosis of the superior sagittal sinus was induced with a bovine thrombin injection via a microcatheter under distal balloon occlusion for 15 minutes. Combined arterial injections and superselective sinus injections confirmed the extent of thrombosis. EVT was subsequently performed using a second-generation stent retriever, followed by intravascular optical coherence tomography (OCT) imaging to assess the luminal environment after thrombectomy.

RESULTS

Thrombosis of the superior sagittal sinus, EVT, and subsequent OCT imaging were technically successful in 4 of the 5 swine. Recanalization of the sinus with a second-generation stent retriever was successful after one attempt in 3 of 4 swine (75%), and 1 swine required two attempts. OCT imaging after thrombectomy revealed regions of residual sinus luminal thrombus despite complete angiographic recanalization. Thrombosed bridging cortical veins were also observed before draining into the sinus, along with patent cortical veins.

CONCLUSIONS

The authors describe a preclinical model to assess endovascular techniques and devices for the treatment of CVST. Repurposed devices from arterial stroke may not perform as expected, given the unique features of venous sinus thrombosis. Residual bridging cortical vein thrombus and residual sinus thrombus, visualized on intravascular OCT, may be present despite complete sinus recanalization on angiography, and this may be the etiology of the poor clinical outcome despite technical success. In the setting of bridging cortical vein thrombus after successful sinus thrombectomy, direct chemical thrombolysis may be warranted to dissolve the remaining clot. This model may be helpful in developing and testing a new generation of devices designed specifically for CVST treatment.

Free access

Ameen Al-Omair, Roger Smith, Tim-Rasmus Kiehl, Louis Lao, Eugene Yu, Eric M. Massicotte, Julia Keith, Michael G. Fehlings, and Arjun Sahgal

Spine stereotactic radiosurgery (SRS) is increasingly being used to treat metastatic spinal tumors. As the experience matures, high rates of vertebral compression fracture (VCF) are being observed. What is unknown is the mechanism of action; it has been postulated but not confirmed that radiation itself is a contributing factor. This case report describes 2 patients who were treated with spine SRS who subsequently developed signal changes on MRI consistent with tumor progression and VCF; however, biopsy confirmed a diagnosis of radiation-induced necrosis in 1 patient and fibrosis in the other. Radionecrosis is a rare and serious side effect of high-dose radiation therapy and represents a diagnostic challenge, as the authors have learned from years of experience with brain SRS. These cases highlight the issues in the new era of spine SRS with respect to relying on imaging alone as a means of determining true tumor progression. In those scenarios in which it is unclear based on imaging if true tumor progression has occurred, the authors recommend biopsy to rule out radiation-induced effects within the bone prior to initiating salvage therapies.

Restricted access

Christopher R. Pasarikovski, Julia Keith, Leodante da Costa, Joel Ramjist, Yuta Dobashi, Sandra E. Black, and Victor X. D. Yang

OBJECTIVE

Although studies have shown that some degree of iatrogenic endothelial injury occurs during endovascular thrombectomy (EVT), the clinical significance of such injury is uncertain. Furthermore, it is likely that iatrogenic effects such as endothelial denudation, intimal dissection, and tunica media edema will have varying clinical implications. The purpose of this study was to assess the feasibility of endovascular optical coherence tomography (OCT) in quantifying vessel injury in real time after EVT, correlate vessel injury with histological findings, and perform imaging at varying time intervals after EVT to assess the impact of prolonged direct exposure of the vessel to the thrombus.

METHODS

Yorkshire swine weighing 35–40 kg were selected for use as the animal model, with a total of 9 vessels from 3 swine examined. Thrombectomy was performed using a second-generation stent retriever 1, 3, and 6 hours after thrombus deposition. The presence and degree of denudation of the endothelium, detachment and separation of the layers of the tunic media, hemorrhage within the media, dissection of the vessels, and thrombus within the lumina were assessed using OCT images acquired immediately after EVT. Bland-Altman analysis indicated that these OCT findings were correlated with postmortem histological findings.

RESULTS

OCT image acquisition was technically successful in all cases. Endothelial denudation was present in 65% ± 16%, 87% ± 8%, and 93% ± 7% of the vessel surface 1, 3, and 6 hours, respectively, after thrombus deposition and subsequent EVT. Residual intraluminal thrombus was present in vessels at all time intervals despite complete angiographic revascularization. Bland-Altman plots showed good agreement between OCT and histological analysis with respect to the degree of endothelial denudation and elevation, separation of the tunica media, and hemorrhage within the media. OCT appears to be more specific than histological analysis in detecting endothelial elevation.

CONCLUSIONS

OCT is a feasible method that can be used to assess vascular injury after EVT with histological accuracy. Varying degrees of vessel injury occur after EVT, and residual luminal thrombus can be present despite complete angiographic revascularization.