Indocyanine green angiography in spinal cord vascular reticulocytoma surgery

Spinal vascular reticulocytoma is a benign tumor that occurs in the spinal cord and is highly vascularized, accounting for about 1-7% of intramedullary tumors. However, due to the rich blood supply of the tumor, it is difficult to identify the blood supplying arteries and draining veins during surgery, and it is also very difficult to locate the tumor and its blood vessels completely within the medulla, which poses great difficulties for total resection and intraoperative bleeding control. In addition, if the main blood supply artery is not completely treated during surgery, the drainage vein may be severely swollen and cause irreversible spinal cord dysfunction, especially in the high cervical spinal cord, which may cause secondary edema or injury in the high spinal cord, leading to respiratory and circulatory disorders and tetraplegia. Therefore, microsurgical treatment of spinal vascular reticulocytoma requires not only skillful, accurate and precise microsurgical skills, but also the ability to accurately determine the blood supplying arteries and draining veins of the tumor during surgery. With the rapid development of neuroimaging and microsurgery techniques, intraoperative indocyanine green fluorescence angiography has begun to be used for monitoring blood flow information in neurosurgery. We summarize the clinical data of intraoperative indocyanine green fluorescence angiography applied in microsurgery of patients with spinal vascular reticulocytoma from 2008 to 2013. Subjects and methods 1. General data Twenty-five patients with spinal cord vascular reticulocytoma treated at the Armed Forces General Hospital from October 2008 to October 2013 were collected, including 18 males and 7 females, aged 21 to 67 years, with an average age of 39.6 years, and a disease duration of 2 months to 4 years, with an average of 15 months. The tumors were located in the cervical segment in 12 cases, the thoracic segment in 8 cases, the lumbosacral segment in 2 cases, and multiple cases in 3 cases, with a maximum of 3 lesions. The first symptoms were limb weakness in 9 cases, pain in 8 cases, sensory disturbance in 7 cases, and subarachnoid hemorrhage in 1 case, among which 5 cases of cervical medullary hemangiopericytoma had simple neck pain and 3 cases of neck pain with radiating pain in one upper limb. All patients underwent MRI with Gd-DTPA enhancement scan, and the spinal cord hemangiopericytoma showed equal or low signal in T1WI and equal or high signal in T2WI. Three patients underwent preoperative digital subtraction angiography (DSA), one of which was an extended cervical segment, and two of which were giant vascular reticulocytomas over 75 px in length. The tumors showed uniform staining in the early arterial stage and continued to the venous stage with clear blood supply arteries and draining veins, and the tumors showed obvious staining clusters. 2.Surgical method Pre-operatively, we need to ask if there is any history of indocyanine green, iodine and other serious allergy, and if necessary, we can conduct indocyanine green allergy test. Patients should sign the consent form for intraoperative application of indocyanine green fluorescence contrast. Preoperatively, the tumor segments were localized according to MRI, and the sphenoid process was precisely positioned with methylene blue injection under X-ray; the lateral prone position was adopted, and the tumor side was adjusted on the operative field according to the tumor site to facilitate the operation, and the tumor in the extended cervical junction and high cervical segment was fixed with three nail heads, etc. The posterior median approach was adopted, and the electric knife was used to cut the muscle along the posterior median line to expose the sphenoid process and both sides of the vertebral plate and fully expose the dura mater, and the dura mater was cut longitudinally under the microscope. The upper and lower poles of the tumor were fully exposed. The tumor should be separated from the tumor by low power bipolar electrocoagulation starting from one side, and the blood supply artery should be cut off while the tumor is separated. After cutting off the blood supply artery and then cut off the drainage vein, the tumor should be removed completely, not in pieces, otherwise it may cause bleeding or even haemorrhage in the tumor section. After resection of the tumor, fluorescence imaging should be performed again to observe whether there is residual tumor and normal blood vessels in the spinal cord. If there is still tumor residue under special circumstances, the surgery can be continued to remove the remaining tumor and fluorescence imaging again after resection until the resection is satisfactory. After strict hemostasis, physiological saline is repeatedly rinsed in the operation area, and the dura mater is tightly sutured to avoid postoperative cerebrospinal fluid leakage and muscle and subcutaneous fluid accumulation, and the spinous process and vertebral plate are repositioned and fixed with two-hole titanium plates to maintain spinal stability. 3, fluorescence imaging method: Pentero German Carl Zeiss operating microscope with fluorescence imaging function is used (fluorescence imaging program software should be installed at the same time). The contrast agent should be indocyanine green for injection (25 mg, Dandong Medtron Pharmaceutical Co., Ltd.). Before imaging, adjust the microscope to the imaging area, adjust the microscope magnification and focal length to the ideal state, and switch the fluorescence angiography mode. The indocyanine green contrast agent (0.2~0.5mg/kg of indocyanine green for injection is dissolved in 2ml of sterilized water for injection, which should be completely dissolved, and the regular dose for adults is 25mg/time) is injected rapidly through the median elbow vein or central venous catheter, and after about 7~10s, the angiographic image starts to appear on the microscope monitor and is automatically recorded. The whole contrast image was divided into arterial phase, capillary phase and venous phase. The contrast fluorescence gradually decays with time and the duration varies, and the angiographic images can be repeatedly played on the monitor. The interval between two angiograms should be at least 15 minutes. 4. Postoperative adjuvant therapy and follow-up evaluation Postoperative patients routinely apply hormone shock therapy and rehabilitation exercises, and McCormick spinal cord functional status grading is used for preoperative and postoperative neurological function evaluation. After discharge from the hospital, outpatient or telephone or internet follow-up was performed, and the follow-up period ranged from 3 to 60 months, with an average of 28 months. Results: All 25 cases of spinal cord hemangiopericytoma were completely resected by microsurgery, and 3 cases of multiple patients were also completely resected by staged surgical resection, and all were pathologically confirmed as hemangiopericytoma. During the surgery, all patients underwent indocyanine green fluorescence imaging before tumor resection to determine the blood supplying arteries and draining veins of the tumor, and again after tumor resection to observe whether there was residual tumor and normal blood vessels in the spinal cord. 3 cases (including 2 cases of preoperative grade I and 1 case of grade II) and 1 case of aggravation, which was grade III before surgery and recovered within 1 month. No tumor recurrence was observed during the follow-up period. After resection of the tumor, fluorescence imaging showed that there was no residual tumor, normal spinal cord vascular morphology and alignment, and no abnormal vascularization. Discussion: Spinal vascular reticulocytoma, also known as hemangioblastoma, is a benign tumor that originates from the embryonic remnants of mesodermal cells and is a true vascular tumor in the spinal cord. Intracranial angioretinomas are more common than spinal angioretinomas, which account for about 1%-7% of spinal cord tumors [1]. Most spinal angioretinomas are solid tumors with varying degrees of spinal edema and dilatation of the central canal of the spinal cord [2-3]. Spinal angioretinal cell tumors can be cured by microsurgery to achieve total resection of the disease. However, complete recovery of spinal cord dysfunction due to the tumor is often difficult. The recovery of spinal cord function in patients is negatively correlated with the degree of preoperative spinal cord dysfunction [4], that is, the more severe the preoperative spinal cord symptoms are, the worse the postoperative recovery is. In clinical practice, we found that the more severe and longer the preoperative spinal cord dysfunction is, the worse the postoperative recovery is. Therefore, early diagnosis and early treatment of spinal cord angioretinal cell tumors are crucial to the recovery of spinal cord function in patients. Accurate identification of the tumor’s blood supply arteries and draining veins is the key to successful surgery, which requires very accurate determination of whether the vessels are draining veins that converge into the venous plexus or blood supply arteries that originate from the anterior and posterior spinal cord arteries. Wrongly disconnecting the normal blood supply arteries of the spinal cord will cause severe spinal cord ischemia, which will lead to severe spinal cord dysfunction; prematurely disconnecting the tumor draining veins may lead to severe spinal cord edema or even severe spinal cord infarction, therefore, intraoperative evaluation of the tumor blood supply arteries and draining veins is very important [5]. MRI is the most valuable diagnostic method of choice for the diagnosis of spinal vascular reticulocytes, and is of great importance for localization and qualitative diagnosis. Spinal angiography is particularly important in patients with atypical MRI findings that are difficult to diagnose and need to be differentiated from other vascular diseases of the spinal cord. Spinal vascular reticulocytoma presents on spinal angiography as a homogeneous staining of the tumor in the early arterial phase, in the form of a mass, which continues into the venous phase, where definite tumor staining is seen. Spinal angiography can not only help to confirm the diagnosis, but also determine the blood supplying arteries and draining veins very precisely, especially for larger tumors that can be considered for preoperative embolization to reduce surgical bleeding [6] and reduce the risk of surgery. Although spinal angiography is the gold standard for the diagnosis of spinal cord vascular diseases, the images it provides lack real-time, dynamic blood flow information and are difficult to represent the morphological characteristics of tumors and blood vessels, while the requirements for equipment, invasiveness, and poor operability due to radiation are rarely used in spinal cord disease surgical procedures. Even because spinal angiography and embolization may cause spasm or even occlusion of normal spinal cord vessels, resulting in severe neurological deficits caused by spinal cord ischemia, and because of the widespread use of intraoperative indocyanine green fluoroscopy in neurosurgery, preoperative spinal angiography and embolization are not necessary [7]. Indocyanine green is a tri-carbon cyanine dye with a maximum absorption wavelength of 805 nm and a maximum fluorescence wavelength of 835 nm, which is excited by near-infrared light to produce fluorescence effects; its good hydrophilicity, not easy to cross the blood-brain barrier, short half-life, good fluorescence performance, very suitable for human intraoperative imaging use. ICG was first authorized by the U.S. Food and Drug Administration in 1956 for heart and liver, and then used for funduscopic imaging. The ICG was first authorized by the FDA in 1956 for use in the heart and liver, and then for fundus imaging. Fluorescence imaging technology was first proposed by Feindel in 1967 to apply indocyanine green angiography to neurosurgery intracranial angiography, and in 2003 Raabb [8] and others first combined ICG angiography with video recording technology to assist surgery, and in 2005 Raabb reported that the operating microscope integrating indocyanine green fluorescence imaging was applied to intracranial aneurysm clamping surgery. The intraoperative ICG fluorescence angiography can help the operator to adjust the aneurysm clamps in time, effectively avoiding incomplete clamping of the aneurysm neck and better protecting the aneurysm-carrying artery and the penetrating vessels. With the combination of this technique and the surgical microscope, fluoroscopy has been widely used in clinical practice, and it is easy and practical, provides real-time blood flow information, has clear images, is highly operable, and is non-radioactive, etc. Fluoroscopy has gradually become a monitoring tool for intraoperative evaluation of blood flow [9-11]. In the last decade, there have been a large number of reports in the literature investigating the practical value of indocyanine green angiography through the experience of its application in the treatment of intracranial and spinal cord vascular diseases. The domestic literature has reported the application of this technique in intracranial aneurysm clamping, intracranial arteriovenous malformation resection, intracranial and extracranial vascular bypass and arteriovenous fistula surgery, and also in brain tumor surgery for real-time dynamic observation of intra- and peritumoral vascular flow. In microsurgery for spinal vascular reticulocytoma, early dissection of the main blood supply artery of the tumor can avoid uncontrollable intraoperative bleeding and avoid accidental injury to the drainage vein, which can cause swelling of the spinal cord and ensure successful surgery. The advantage of fluorescence imaging is also reflected in the fact that after the tumor is resected, the fluorescence imaging again shows whether there is any residual tumor in the resection area [12]. All patients in this group applied indocyanine green fluorescence imaging intraoperatively, with clear images and high resolution, clearly showing tumor morphology, blood supply arteries and draining veins (Figure C and D of typical cases), and helping the operator to determine the location of tumor, blood supply arteries and draining veins in time. The integration of indocyanine green fluorescence imaging and surgical microscope not only does not affect the microsurgical operation, but also can quickly and real-time determine the vascular situation and adjust the surgical plan according to the imaging results, which has a strong timeliness; at the same time, it has a high spatial resolution, which can display the blood vessels below 0.5mm in diameter, and the microscopic vessels that cannot be displayed by DSA can be displayed by indocyanine green fluorescence imaging. However, it has some limitations in surgical operation, as the recorded image can only be confined to the microscopic field of view, and only directly exposed vessels can be displayed. Therefore, in microsurgery of spinal cord vascular reticulocytoma, because indocyanine green fluorescence imaging can only show the morphology of the tumor in the microscopic field and the directly exposed vessels in the periphery, but cannot reflect the vascular situation inside the tumor. Therefore, it is necessary to keep the field clean and tidy before intraoperative fluoroscopy and ensure that there is no relevant obstruction in the field (Figure A and B of typical cases). Indocyanine green fluorescence imaging is used to determine the blood supply artery and drainage vein of the tumor in spinal cord angioretinoma surgery, so as to guide the operator to accurately deal with the blood supply artery and drainage vein and avoid the occurrence of uncontrollable bleeding and severe spinal cord swelling during surgery. After surgical resection of the tumor, fluoroscopy can be performed again to evaluate the extent of surgical resection and normal blood vessels of the spinal cord; according to the imaging results, the residual tumor can be resected if necessary, thus improving the success rate of total resection and avoiding tumor recurrence after surgery.