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Background: Near-infrared fluorescence (NIRF) imaging has recently emerged as a promising tool for noninvasive cancer imaging. However, lack of tumor sensitivity and specificity restricts the application of NIRF dyes in surgical navigation. Methods: Herein, we investigated the imaging features of NIRF dye MHI-148 and indocyanine green (ICG) in live cell imaging and xenograft nude mice models. TCGA dataset analysis and immunohistochemistry were conducted to investigate the expression of OATPs or ABCGs in hepatocellular carcinoma (HCC) tissues. OATPs or ABCGs were knocked down and overexpressed in HCC cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Further, qRT-PCR ,Western blotting and the use of agonists or inhibitors targeting ß-catenin signaling pathway were applied to explore its important role in regulation of OATP2B1 and ABCG2 expression. Results: Here we demonstrated that NIRF dye MHI-148 was biocompatible as indocyanine green (ICG) but with higher imaging intensity and preferential uptake and retention in hepatocellular carcinoma (HCC) cells and tissues. Moreover, our data indicated that membrane transporters OATP2B1 and ABCG2, which regulated by ß-catenin signaling pathway, mediated tumor-specific accumulation and retention of MHI-148 in HCC cells. In addition, the treatment with ß-catenin inhibitor significantly enhanced the accumulation of MHI-148 in HCC tissues and improved the efficacy of tumor imaging with MHI-148 in vivo. Conclusions: Our study uncovers a mechanism that links the distribution and expression of the membrane transporters OATP2B1 and ABCG2 to the tumor-specific accumulation of MHI-148, and provides evidence supporting a regulating role of the ß-catenin signaling pathway in OATP2B1 and ABCG2- induced retention of MHI-148 inHCC tissues, and strategy targeting key components of MHI-148 transport machinery may be a potential approach to improve HCC imaging.
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Objective: Assess the surgeons' workload during deep endometriosis surgery after ureteral ICG. Design: Prospective, consecutive, comparative, single-center study. Population: 41 patients enrolled to deep endometriosis surgery with ureteral ICG from January 2019 to July 2021 at La Paz University Hospital. Methods: Patients were divided into 2 groups: patients operated during the learning curve of ureteral ICG instillation and patients operated after the technique was implemented and routinely performed. After surgery, the SURG-TLX form was completed by the surgeons. We evaluated whether a workload reduction occurred. Main outcomes measures: Surgeon's workload was measured using the SURG-TLX form, obtaining the total workload and 6 different dimensions (distractions, temporal demands, task complexity, mental demands, situational stress and physical demands). Results: A significant positive correlation was found between surgical complexity and situational stress (p = 0.04). Mental demands (p = 0.021), physical demands (p = 0.03), and total workload (p = 0.025) were significantly lower when the technique was routinely performed. The mental demand, physical demands, and total workload perceived by the surgeons at the beginning of the implementation was higher (68 [39-72], 27 [11-46.5], 229 [163-240], respectively) than in the latter ones (40 [9-63], 11.5 [0-32.8], 152 [133.3-213.8], respectively). Distractions appeared to be higher in the latter surgeries (8.5 [0-27.8]) than in the first surgeries (0 [0-7]; p = 0.057). Conclusions: Ureter ICG instillation prior to DE surgery significantly reduces the mental and physical demands and total workload of the surgeons in DE surgeries after overcoming the learning curve. Distractions appear to increase as surgical stress decreases.
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BACKGROUND: Sufficient understanding of the angioarchitecture of an arteriovenous fistula (AVF) at the craniocervical junction (CCJ) is crucial to surgical treatment but is often difficult because of the complex vascular anatomy. Intraarterial indocyanine green (ICG) videoangiography has emerged as a more useful option for understanding the vascular anatomy than intravenous ICG videoangiography. This report describes two cases of CCJ AVFs successfully treated by surgery using intraarterial ICG videoangiography and describes the efficacy of this technique. OBSERVATIONS: Case 1 involved a 71-year-old man presenting with tetraparesis after sudden onset of severe headache due to subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) demonstrated CCJ epidural AVF. Intraarterial ICG videoangiography revealed the drainer, which had been difficult to identify. The AVF disappeared after disconnection of the drainer. Case 2 involved a 68-year-old man presenting with severe headache due to SAH. DSA showed multiple AVFs at the CCJ and cerebellar tentorium. Intraarterial ICG videoangiography demonstrated concomitant perimedullary AVF and dural AVF at the CCJ. All AVFs disappeared postoperatively. LESSONS: Intraarterial ICG videoangiography was useful for definitive diagnosis of CCJ AVF, facilitating identification of feeders and drainers with bright and high phase contrast and allowing repeated testing to confirm flow direction.
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Indocyanine green (ICG) is a nontoxic registered photosensitizer used as a diagnostic tool and for photodynamic therapy (PDT). Hypoxia is one the main factors affecting PDT efficacy. Perfluorodecalin emulsion (Perftoran®) is a known oxygen carrier. This study investigated the effect of Perftoran® on ICG/PDT efficacy in presence and absence of Perftoran® via evaluation of phototoxicity by MTT; hypoxia estimation by pimonidazole, HIF-1α/ß by ELISA, and 17 miRNAs (tumor suppressors, oncomiRs, and hypoxamiRs) were analyzed by qPCR. Compared to ICG/PDT, Perftoran®/ICG/PDT led to higher photocytotoxicity, inhibited pimonidazole hypoxia adducts, inhibited HIF-1α/ß concentrations, induced the expression of tumor-suppressing miRNAs let-7b/d/f/g, and strongly inhibited the pro-hypoxia miRNA let-7i. Additionally, Perftoran®/ICG/PDT suppressed the expression of the oncomiRs miR-155, miR-30c, and miR-181a and the hypoxamiRs miR-210 and miR-21 compared to ICG/PDT. In conclusion, Perftoran® induced the phototoxicity of ICG/PDT and inhibited ICG/PDT-hypoxia via suppressing HIF-α/ß, miR-210, miR-21, let-7i, miR-15a, miR-30c, and miR-181a and by inducing the expression of let-7d/f and miR-15b.
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BACKGROUND: The bonnet bypass was initially described for common carotid artery occlusion. Considered a second-generation bypass, it augments intracranial perfusion with contralateral external carotid artery flow through an interposition graft running over the scalp vertex. However, the traditional first-generation low-flow superficial temporal artery (STA)-M4 middle cerebral artery (MCA) bypass may be enhanced by performing a side-to-side (S-S) bypass with an intraluminal suture technique (fourth-generation bypass) to increase perfusion through antegrade and retrograde flow. OBSERVATIONS: The authors present a reimagined S-S STA-M4 bypass in the case of a patient with symptomatic common carotid occlusion, in which the ipsilateral STA filled in a reverse fashion from the contralateral external carotid branches over the scalp vertex (bonnet collaterals). By performing an S-S anastomosis, the authors were able to improve cerebral perfusion and avoid the multiple anastomosis sites of the bonnet bypass. LESSONS: The patient had a good recovery with resolution of his preoperative symptoms. Follow-up angiography showed a patent bypass supplying the MCA territory through retrograde flow in the frontal and parietal limbs of the STA, converging at the anastomosis site. In this report, the authors present a new fourth-generation bypass dubbed the "S-S reverse STA-M4 MCA bypass."
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BACKGROUND: Arteriovenous malformation (AVM) of the trigeminal nerve root (TNR) is a rare subtype of the lateral pontine AVM. Most of them are diagnosed when they bleed or exert trigeminal neuralgia. Venous congestive edema is a rare phenomenon caused by TNR AVMs. OBSERVATIONS: An 82-year-old man was admitted with progressive limb weakness and dysphasia. Magnetic resonance imaging (MRI) revealed extensive edema of the medulla oblongata and the upper cervical cord with signal flow void at the C3 anterior spinal cord. Vertebral angiography revealed a small nidus fed mainly by the pontine perforating arteries (PPAs). The anterior pontomesencephalic vein (AMPV) was dilated, functioning as the main drainage route. This suggests that venous hypertension triggered the brainstem and upper cervical cord edema. MRI with gadolinium enhancement showed that the nidus was located around the right TNR. Because the nidus sat extrinsically on the pial surface of the right TNR's base, microsurgical obliteration with minimum parenchymal injury was achieved. Postoperative MRI showed disappearance of the brainstem and cervical cord edema with improved clinical symptoms. LESSONS: TNR AVM is rarely associated with brainstem and upper cervical cord edema caused by venous hypertension of the congestive drainage system.
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BACKGROUND: Spinal dural arteriovenous fistulas (SDAVFs) are rare vascular malformations of the spine but account for up to 80% of all vascular malformations involving the spine. Few case reports of SDAVFs have been reported in the literature, and even fewer have been described with sudden onset of symptoms. OBSERVATIONS: The authors described the case of a 72-year-old male with sudden-onset bilateral paraplegia and sensory loss with subsequent inability to bear weight and an initial suspicion of cauda equina syndrome, which was eventually diagnosed as an SDAVF using magnetic resonance imaging. During open surgery, it was difficult to identify the feeder vessels. A postoperative scan showed persistence of the fistula, and the patient had to receive redo ligation with good postoperative status. LESSONS: Sudden-onset paraplegia is not the typical presentation of SDAVF. All doctors need to be aware of the possibility of an acute presentation with SDAVF, especially with the high likelihood of misdiagnosis and resultant worse outcome due to treatment delays. A high index of suspicion is required to ensure early recognition as well as initiation of treatment.
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BACKGROUND: Unlike in aneurysms of the adult-type posterior cerebral artery (PCA), in aneurysms of the fetal-type PCA, parent artery occlusion (PAO) results in vascular insufficiency and major ischemic strokes. Preservation or reconstruction of fetal-type PCAs is necessary to prevent these complications. Furthermore, it is necessary to select an appropriate bypass method and approach for revascularization of the PCA. OBSERVATIONS: The authors report 2 cases of aneurysms of fetal-type PCAs that were successfully treated with PAO with revascularization. A 38-year-old man with a large unruptured right PCA aneurysm at the postcommunicating (P2) segment underwent trapping with superficial temporal artery-PCA bypass via the anterior temporal and subtemporal approaches. In addition, a 45-year-old woman with a left PCA aneurysm at the quadrigeminal (P3)-cortical (P4) segments resulting in subarachnoid hemorrhage underwent proximal clipping of the P3 segment via the occipital interhemispheric approach with an occipital artery-PCA bypass. Although she had perforator infarction, major ischemic stroke was prevented, and aneurysm occlusion was accomplished in both cases. LESSONS: Aneurysms of fetal-type PCAs pose a risk of ischemia due to PAO. The combined use of bypass and revascularization should be considered to prevent major ischemic stroke after occlusion of the fetal-type PCA. However, perforator infarction is a concern.
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BACKGROUND: Angiogram-negative nontraumatic subarachnoid hemorrhage (SAH) can be diagnostically challenging, and a broad differential diagnosis must be considered. Particular attention to initial radiographic hemorrhage distribution is essential to guide adjunctive investigations. Posterior spinal artery aneurysms are rare clinical entities with few reported cases in the literature. An understanding of isolated spinal artery aneurysm natural history, diagnosis, and management is evolving as more cases are identified. OBSERVATIONS: Isolated thoracic posterior spinal artery aneurysm can be the culprit lesion in perimesencephalic distribution SAH. Embolization resulted in complete aneurysm occlusion and did not result in periprocedural morbidity. At the 1-year follow-up, the patient was neurologically intact with no recurrence on magnetic resonance angiography. LESSONS: This case report highlighted the presentation, diagnostic workup, clinical decision-making, and endovascular intervention for a woman who presented with SAH secondary to posterior spinal artery aneurysm. After initially negative results on vascular imaging, dedicated spinal vascular imaging revealed the location of the aneurysm. Multiple treatment modalities exist for isolated spinal artery aneurysms and must be selected on the basis of patient- and lesion-specific characteristics.
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BACKGROUND: When performing clip ligation of superior projecting aneurysms of the proximal (M1) segment of the middle cerebral artery (MCA), meticulous sylvian fissure dissection alone may be inadequate for safe clip application, especially in cases in which the aneurysm is buried in the limen recess, since the limen insulae may be positioned lateral to the aneurysm. In the present patient series, the authors present their surgical technique for clip ligation of aneurysms located in the limen recess, with partial resection of the limen insulae. OBSERVATIONS: A retrospective analysis of patients who had undergone clip ligation of MCA aneurysms located at the limen recess at a single institute was performed. Patients with angiographic and clinical follow-up data were considered eligible. A total of 11 aneurysms (4 ruptured and 7 unruptured aneurysms) in 11 patients were evaluated. Postoperative ischemic lesions were observed on images obtained within 1 week after surgery in 5 (45.5%) patients who had undergone partial resection of the limen insulae, although none of them presented with neurological deterioration. LESSONS: Partial resection of limen insulae may be feasible to avoid severe ischemic complications following clip ligation of M1 aneurysms embedded in the limen recess.
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OBJECTIVE: The use of endoscope-integrated indocyanine green (E-ICG) has recently been introduced in skull base surgery. The quantitative correlation between E-ICG and T1-weighted gadolinium-enhanced (T1WGd) images for skull base tumors has not been previously assessed, to the authors' knowledge. In this study, the authors investigated the indications for use and the limitations of E-ICG and sought to correlate the endoscopic fluorescence pattern with MRI contrast enhancement. METHODS: Following IRB approval, 20 patients undergoing endoscopic endonasal skull base surgery between June 2017 and August 2018 were enrolled in the study. Tumor fluorescence was measured using a blue color value and blood fluorescence as a control. Signal intensities (SIs) of tumor T1WGd images were measured and the internal carotid artery (ICA) SI was used as a control. For pituitary adenoma, the pituitary gland fluorescence was also measured. The relationships between ICG fluorescence and MRI enhancement measurements were analyzed. RESULTS: Data showed that in pituitary adenoma there was a strong correlation between the ratios of gland/blood fluorescence to gland/ICA SI (n = 8; r = 0.92; p = 0.001) and tumor/blood fluorescence to tumor/ICA SI (n = 9; r = 0.82; p = 0.006). In other pathologies there was a strong correlation between the ratios of tumor/blood fluorescence and tumor/ICA SI (n = 9; r = 0.74; p = 0.022). The ICG fluorescence allowed perfusion assessment of the pituitary gland as well as of the nasoseptal flaps. Visualization of the surrounding vasculature was also feasible. CONCLUSIONS: Defining the indications and understanding the limitations are critical for the effective use of E-ICG. Tumor fluorescence seems to correlate with preoperative MRI contrast enhancement.
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OBJECTIVE: Incomplete resection of skull base pathology may result in local tumor recurrence. This study investigates the utility of 5-aminolevulinic acid (5-ALA) fluorescence during endoscopic endonasal approaches (EEAs) to increase visibility of pathologic tissue. METHODS: This retrospective multicenter series comprises patients with planned resection of an anterior skull base lesion who received preoperative 5-ALA at two tertiary care centers. Diagnostic use of a blue light endoscope was performed during EEA for all cases. Demographic and tumor characteristics as well as fluorescence status, quality, and homogeneity were assessed for each skull base pathology. RESULTS: Twenty-eight skull base pathologies underwent blue-light EEA with preoperative 5-ALA, including 15 pituitary adenomas (54%), 4 meningiomas (14%), 3 craniopharyngiomas (11%), 2 Rathke's cleft cysts (7%), as well as plasmacytoma, esthesioneuroblastoma, and sinonasal squamous cell carcinoma. Of these, 6 (21%) of 28 showed invasive growth into surrounding structures such as dura, bone, or compartments of the cavernous sinus. Tumor fluorescence was detected in 2 cases (7%), with strong fluorescence in 1 tuberculum sellae meningioma and vague fluorescence in 1 pituicytoma. In all other cases fluorescence was absent. Faint fluorescence of the normal pituitary gland was seen in 1 (7%) of 15 cases. A comparison between the particular tumor entities as well as a correlation between invasiveness, WHO grade, Ki-67, and positive fluorescence did not show any significant association. CONCLUSIONS: With the possible exception of meningiomas, 5-ALA fluorescence has limited utility in the majority of endonasal skull base surgeries, although other pathology may be worth investigating.
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OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical management for moyamoya disease (MMD), whereas cerebral hyperperfusion (CHP) is one of the potential complications of this procedure that can result in delayed intracerebral hemorrhage and/or neurological deterioration. Recent advances in perioperative management in the early postoperative period have significantly reduced the risk of CHP syndrome, but delayed intracerebral hemorrhage and prolonged/delayed CHP are still major clinical issues. The clinical implication of RNF213 gene polymorphism c.14576G>A (rs112735431), a susceptibility variant for MMD, includes early disease onset and a more severe form of MMD, but its significance in perioperative pathology is unknown. Thus, the authors investigated the role of RNF213 polymorphism in perioperative hemodynamics after STA-MCA anastomosis for MMD. METHODS: Among 96 consecutive adult patients with MMD comprising 105 hemispheres who underwent serial quantitative cerebral blood flow (CBF) analysis by N-isopropyl-p-[123I]iodoamphetamine SPECT after STA-MCA anastomosis, 66 patients consented to genetic analysis of RNF213. Patients were routinely maintained under strict blood pressure control during and after surgery. The local CBF values were quantified at the vascular territory supplied by the bypass on postoperative days (PODs) 1 and 7. The authors defined the radiological CHP phenomenon as a local CBF increase of more than 150% compared with the preoperative values, and then they investigated the correlation between RNF213 polymorphism and the development of CHP. RESULTS: CHP at POD 1 was observed in 23 hemispheres (23/73 hemispheres [31.5%]), and its incidence was not statistically different between groups (15/41 [36.6%] in RNF213-mutant group vs 8/32 [25.0%] in RNF213-wild type (WT) group; p = 0.321). CHP on POD 7, which is a relatively late period of the CHP phenomenon in MMD, was evident in 9 patients (9/73 hemispheres [12.3%]) after STA-MCA anastomosis. This prolonged/delayed CHP was exclusively observed in the RNF213-mutant group (9/41 [22.0%] in the RNF213-mutant group vs 0/32 [0.0%] in the RNF213-WT group; p = 0.004). Multivariate analysis revealed that RNF213 polymorphism was significantly associated with CBF increase on POD 7 (OR 5.47, 95% CI 1.06-28.35; p = 0.043). CONCLUSIONS: Prolonged/delayed CHP after revascularization surgery was exclusively found in the RNF213-mutant group. Although the exact mechanism underlying the contribution of RNF213 polymorphism to the prolonged/delayed CBF increase in patients with MMD is unclear, the current study suggests that genetic analysis of RNF213 is useful for predicting the perioperative pathology of patients with MMD.
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OBJECTIVE: Myelopathy selectively involving the lower extremities can occur secondary to spondylotic changes, tumor, vascular malformations, or thoracolumbar cord ischemia. Vascular causes of myelopathy are rarely described. An uncommon etiology within this category is diaphragmatic crus syndrome, in which compression of an intersegmental artery supplying the cord leads to myelopathy. The authors present the operative technique for treating this syndrome, describing their experience with 3 patients treated for acute-onset lower-extremity myelopathy secondary to hypoperfusion of the anterior spinal artery. METHODS: All patients had compression of a lumbar intersegmental artery supplying the cord; the compression was caused by the diaphragmatic crus. Compression of the intersegmental artery was probably producing the patients' symptoms by decreasing blood flow through the artery of Adamkiewicz, causing lumbosacral ischemia. RESULTS: All patients underwent surgery to transect the offending diaphragmatic crus. Each patient experienced substantial symptom improvement, and 2 patients made a full neurological recovery before discharge. CONCLUSIONS: Diaphragmatic crus syndrome is a rare or under-recognized cause of ischemic myelopathy. Patients present with episodic acute-on-chronic lower-extremity paraparesis, gait instability, and numbness. Angiography confirms compression of an intersegmental artery that gives rise to a dominant radiculomedullary artery. Transecting the offending diaphragmatic crus can produce complete resolution of neurological symptoms.
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OBJECTIVE: Vascular malformations of the cervical spine are exceedingly rare. To date there have been no large case series describing the clinical presentation and angioarchitectural characteristics of cervical spine vascular malformations. The authors report their institutional case series on cervical spine vascular malformations diagnosed and treated at their institution. METHODS: The authors retrospectively reviewed all patients with spinal vascular malformations from their institution from January 2001 to December 2018. Patients with vascular malformations of the cervical spine were included. Lesions were characterized by their angioarchitectural characteristics by an interventional neuroradiologist and endovascular neurosurgeon. Data were collected on clinical presentation, imaging findings, treatment outcomes, and long-term follow-up. Descriptive statistics are reported. RESULTS: Of a total of 213 patients with spinal vascular malformations, 27 (12.7%) had vascular malformations in the cervical spine. The mean patient age was 46.1 ± 21.9 years and 16 (59.3%) were male. The most common presentations were lower-extremity weakness (13 patients, 48.1%), tetraparesis (8 patients, 29.6%), and lower-extremity sensory dysfunction (7 patients, 25.9%). Nine patients (33.3%) presented with hemorrhage. Fifteen patients (55.6%) had modified Rankin Scale scores of 0-2 at the time of diagnosis. Regarding angioarchitectural characteristics, 8 patients (29.6%) had intramedullary arteriovenous malformations (AVMs), 5 (18.5%) had epidural arteriovenous fistulas (AVFs), 4 (14.8%) had paraspinal fistulas, 4 (14.8%) had mixed epidural/intradural fistulas, 3 (11.1%) had perimedullary AVMs, 2 (7.4%) had dural fistulas, and 1 patient (3.7%) had a perimedullary AVF. CONCLUSIONS: This retrospective study of 27 patients with cervical spine vascular malformations is the largest series to date on these lesions. The authors found substantial angioarchitectural heterogeneity with the most common types being intramedullary AVMs followed by epidural AVFs, paraspinal fistulas, and mixed intradural/extradural fistulas. Angioarchitecture dictated the clinical presentation as intradural shunts were more likely to present with hemorrhage and acute onset myelopathy, while dural and extradural shunts presented as either incidental lesions or gradually progressive congestive myelopathy.
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Spinal dural arteriovenous fistulas are diagnostically challenging lesions, and they are not well described in patients with a history of a spinal deformity correction. The authors present the challenging case of a 74-year-old woman who had previously undergone correction of a spinal deformity with subsequent revision. Several years after the last deformity operation, she developed a progressive myelopathy with urinary incontinence over a 6-month period. After evaluation at the authors' institution, an angiogram was obtained, demonstrating a fistula at the T12-L1 region. Surgical ligation of the fistula was performed with subsequent improvement of the neurological symptoms. This case is thought to represent the first fistula documented in an area of the spine that had previously been operated on, and to the authors' knowledge, it is the first case report to be associated with spinal deformity surgery. A brief historical overview and review of the pathophysiology of spinal dural arteriovenous fistulas is also included.
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Direct bypass has been used to salvage failed endovascular treatment; however, little is known of the reversed role of endovascular management for failed bypass.The authors report the case of a 7-year-old patient who underwent a superficial temporal artery to middle cerebral artery (STA-MCA) bypass for treatment of a giant MCA aneurysm and describe the role of endovascular rescue in this case. Post-bypass catheter angiogram showed occlusion of the proximal extracranial STA donor with patent anastomosis, possibly due to STA dissection. A self-expanding Neuroform Atlas stent was deployed across the dissection flap, and follow-up images showed revascularization of the STA with good MCA runoff.This case demonstrates that direct extracranial-intracranial bypass failure can infrequently originate from the STA donor vessel and that superselective angiogram can be useful for identification and treatment in such cases. With more advanced endovascular techniques the tide has turned in the treatment of complex cerebrovascular cases, with this case being an early example of successful rescue stenting for endovascular management of a failed donor after STA-MCA bypass.
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The authors report the case of a 78-year-old man with a craniocervical junction epidural arteriovenous fistula who presented with subarachnoid hemorrhage from a ruptured anterior spinal artery (ASA) aneurysm. Because endovascular embolization was difficult, a posterolateral approach was chosen and a novel endoscopic fluorescence imaging system was utilized to clip the aneurysm. The fluorescence imaging system provided clear and magnified views of the ventral spinal cord simultaneously with the endoscope-integrated indocyanine green videoangiography, which helped safely obliterate the ASA aneurysm. With the aid of this novel imaging system, surgeons can appreciate and manipulate complex vascular pathologies of the ventral spinal cord through a posterolateral approach, even when the lesion is closely related to the ASA.
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Blood oxygenation level-dependent functional MRI cerebrovascular reactivity (BOLD-CVR) is a contemporary technique to assess brain tissue hemodynamic changes after extracranial- intracranial (EC-IC) bypass flow augmentation surgery. The authors conducted a preliminary study to investigate the feasibility and safety of intraoperative 3-T MRI BOLD-CVR after EC-IC bypass flow augmentation surgery. Five consecutive patients selected for EC-IC bypass revascularization underwent an intraoperative BOLD-CVR examination to assess early hemodynamic changes after revascularization and to confirm the safety of this technique. All patients had a normal postoperative course, and none of the patients exhibited complications or radiological alterations related to prolonged anesthesia time. In addition to intraoperative flow measurements of the bypass graft, BOLD-CVR maps added information on the hemodynamic status and changes at the brain tissue level. Intraoperative BOLD-CVR is feasible and safe in patients undergoing EC-IC bypass revascularization. This technique can offer immediate hemodynamic feedback on brain tissue revascularization after bypass flow augmentation surgery.
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Revascularización Cerebral/métodos , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/metabolismo , Monitorización Neurofisiológica Intraoperatoria/métodos , Imagen por Resonancia Magnética/métodos , Consumo de Oxígeno/fisiología , Anciano , Circulación Cerebrovascular/fisiología , Trastornos Cerebrovasculares/cirugía , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: Intraoperative molecular imaging with tumor-targeted fluorescent dyes can enhance resection rates. In contrast to visible-light fluorophores (e.g., 5-aminolevulinic-acid), near-infrared (NIR) fluorophores have increased photon tissue penetration and less contamination from tissue autofluorescence. The second-window ICG (SWIG) technique relies on passive accumulation of indocyanine green (ICG) in neoplastic tissues. OTL38, conversely, targets folate receptor overexpression in nonfunctioning pituitary adenomas. In this study, we compare the properties of these 2 modalities for NIR imaging of pituitary adenomas to better understand the potential for NIR imaging in neurosurgery. METHODS: A total of 39 patients with pituitary adenomas were enrolled between June 2015 and January 2018 in 2, sequential, IRB-approved studies. Sixteen patients received systemic ICG infusions 24 hours prior to surgery, and another 23 patients received OTL38 infusions 2-3 hours prior to surgery. NIR fluorescence signal-to-background ratio (SBR) was recorded during and after resection. Immunohistochemistry was performed on the 23 adenomas resected from patients who received OTL38 to assess expression of folate receptor-alpha (FRα). RESULTS: All 16 adenomas operated on after ICG administration demonstrated strong NIR fluorescence (mean SBR 4.1 ± 0.69 [SD]). There was no statistically significant difference between the 9 functioning and 7 nonfunctioning adenomas (p = 0.9). After administration of OTL38, the mean SBR was 1.7 ± 0.47 for functioning adenomas, 2.6 ± 0.91 for all nonfunctioning adenomas, and 3.2 ± 0.53 for the subset of FRα-overexpressing adenomas. Tissue identification with white light alone for all adenomas demonstrated 88% sensitivity and 90% specificity. SWIG demonstrated 100% sensitivity but only 29% specificity for both functioning and nonfunctioning adenomas. OTL38 was 75% sensitive and 100% specific for all nonfunctioning adenomas, but when assessment was limited to the 9 FRα-overexpressing adenomas, the sensitivity and specificity of OTL38 were both 100%. CONCLUSIONS: Intraoperative imaging with NIR fluorophores demonstrates highly sensitive detection of pituitary adenomas. OTL38, a folate-receptor-targeted fluorophore, is highly specific for nonfunctioning adenomas but has no utility in functioning adenomas. SWIG, which relies on passive diffusion into neoplastic tissue, is applicable to both functioning and nonfunctioning pituitary adenomas, but it is less specific than targeted fluorophores. Thus, targeted and nontargeted NIR fluorophores play important, yet distinct, roles in intraoperative imaging. Selectively and intelligently using either agent has the potential to greatly improve resection rates and outcomes for patients with intracranial tumors.