Information-guided Surgery Centered on Intraoperative Magnetic Resonance Imaging Guarantees Surgical Safety with Low Mortality

Abstract

Neurosurgery is complex surgery that requires a strategy that maximizes the removal of tumors and minimizes complications; thus, a safe environment during surgery should be guaranteed. In this study, we aimed to verify the safety of brain surgery using intraoperative magnetic resonance imaging (iMRI), based on surgical experience since 2000. Thus, we retrospectively examined 2,018 surgical procedures that utilized iMRI performed in the operating room at Tokyo Women's Medical University Hospital between March 2000 and October 2019. As per our data, glioma constituted the majority of the cases (1,711 cases, 84.8%), followed by cavernous hemangioma (61 cases, 3.0%), metastatic brain tumor (37 cases, 1.8%), and meningioma (31 cases, 1.5%). In total, 1,704 patients who underwent glioma removal were analyzed for mortality within 30 days of surgery and for reoperation rates and the underlying causes within 24 hours and 30 days of surgery. As per our analysis, only one death out of all the glioma cases (0.06%) was reported within the 30-day period. Meanwhile, reoperation within 30 days was performed in 37 patients (2.2%) due to postoperative bleeding in 17 patients (1.0%), infection in 12 patients (0.7%), hydrocephalus in 6 patients (0.4%), cerebrospinal fluid (CSF) leakage in 1 patient, and brain edema in 1 patient (0.06%). Of these, 14 cases (0.8%) of reoperation were performed within 24 hours, that is, 13 cases (0.8%) due to postoperative bleeding and 1 case (0.06%) due to acute hydrocephalus. Mortality rate within 30 days was less than 0.1%. Thus, information-guided surgery with iMRI can improve the safety of surgical resections, including those of gliomas.

Introduction

With the accumulated evidence showing the correlation between the extent of resection (EOR) of the tumor and prognosis,^1-4) the current standard surgical treatment for diffuse gliomas is the maximum safe resection of the tumor.^1,5,6) The usefulness of intraoperative magnetic resonance imaging (iMRI) has been reported for reliable and safe removal of not only gliomas but also cavernous hemangiomas and pituitary adenomas.^7-9) However, aiming for maximum lesion removal can increase the risk of neurological deficit due to damage of the surrounding normal brain tissue. Therefore, to achieve maximum removal and, at the same time, preserve neurological function, various modalities and surgical techniques, such as iMRI; the navigation system; awake craniotomy; neuromonitoring, including motor evoked potential (MEP), sensory evoked potential (SEP), and visual evoked potential (VEP); and intraoperative flow cytometry, have been introduced.^10-17)

In addition to functional damage due to surgery, complications such as postoperative bleeding sometimes require reoperation, which often affects the prognosis of patients.^18-24) As per previous reports, the probability of reoperation after brain tumor surgery is at 2.6-17%.^18,22,25-27) Intraoperative support systems, including iMRI, may be able to minimize such complications.^6,28-30) However, there are only a few reports evaluating how intraoperative support systems, such as iMRI, contribute to the safety of neurosurgery.^{6,12,16,29-31)} In our institute, an information-guided operating room was established in 2000 to achieve safe and maximal removal of brain tumors. In recent years, information-guided surgery, which is known to utilize intraoperative anatomical, functional, and histological information in surgery, has developed into a fundamentally different procedure from the traditional technique performed by a surgeon. Since then, about 2,000 cases of brain surgery have been performed at our institute.^2,10,32-34) In this retrospective study, we aimed to evaluate the safety of this system by examining the incidence and causes of reoperations, especially for glioma resections, as they represented the majority of the cases with more than 2,000 operations performed in our information-guided operating room. We have also evaluated cases in which iMRI detected abnormalities, such as intraoperative bleeding, with appropriate intervention immediately given to prevent postoperative complications and reoperation at a later time.

Materials and Methods

This retrospective study was approved by the ethics committees of Tokyo Women's Medical University, Japan (3540-R6). Written informed consent was waived due to the retrospective nature of this study.

We have consistently advocated for objective and reproducible information-based surgery, or the so-called information-guided surgery, to improve surgical success rates. The intelligent operating room was built based on this concept. Our institute developed an intelligent operating room equipped with a low magnetic field (0.3 T) iMRI (Hitachi, Tokyo) in 2000. In 2013, we updated the iMRI to a new 0.4 T low-field MRI. For patients with suspected diffuse glioma, all patients, except for some who required emergency surgery, underwent resection in this operating room without patient selection. Data were collected on all patients treated surgically in the intelligent operating room between March 2000 and October 2019, including those with non-glioma diseases. However, this present analysis of the safety of information-guided surgery using iMRI has focused on the advantages and disadvantages of glioma resection, as it represented the majority of cases, under iMRI use. Specifically, past medical records, radiological images, pathological diagnoses, and surgical records were collected. Information with regard to reoperation rate within 30 days of surgery, reason for surgery, surgical procedure, rate of emergency reoperation within 24 hours of surgery, cause of reoperation, and operation details were examined. We have also evaluated the patient mortality rate within 30 days of surgery and the number of patients who underwent re-excision because of insufficient lesion removal. Postoperative mortality includes unfavorable deaths associated with perioperative complications, such as deep vein thrombosis.

Unplanned reoperation was defined as a case in which reoperation had to be performed due to postsurgical complications, such as postoperative bleeding, infection, increased intracranial pressure, or cerebrospinal fluid (CSF) leakage.

Surgical strategy for diffuse gliomas in the intelligent operating room with iMRI

We usually perform at least three T1- and T2-weighted MRI scans intraoperatively for brain tumor surgery. Gadolinium is often used for enhanced tumors. The first MRI is performed after craniotomy; then, these MRI data are utilized for the navigation system to minimize the effect of brain shift. We used the updated navigation using the first iMRI data for tumor removal; neuromonitoring, including transcortical and transcranial MEP, SEP, and VEP; and awake craniotomy for patients with eloquent area tumors. Meanwhile, the second MRI is performed after tumor removal to check the EOR and location of the residual tumor. If significant residual tumor was detected, which can be removed without a significant risk of neurological deficit, we remove the tumor with updated navigation using the second MRI data. We then continue this process until no residual tumor is detected on the MRI. The same method is used for intraparenchymal lesions such as cavernous hemangiomas and metastatic brain tumors. Indeed, iMRI is useful for lesion removal as it plays a key role in the monitoring and navigation during surgery. After closure, before removing the clean drape, a final MRI scan is performed to detect any possible complication, such as postoperative bleeding. If a problem is determined that requires surgical intervention, a craniotomy is performed again to address it.

Results

Between March 2000 and October 2019, a total of 2,018 surgeries were performed in the intelligent operating room. Of these cases, emergency surgery was performed in 142 cases (7.0%). The average age of patients who underwent surgery was 42.6 years, with a median of 41 (range: 1-84) years. In total, there were 138 cases (6.8%) of children under 20 years of age. Awake surgery was performed in 487 cases (24.1%). iMRI was performed in 2015 (99.9%) cases, excluding 3 cases (0.1%) in which MRI data acquisition was not possible due to issues with the MRI equipment. The average number of iMRI scans performed for one operation was 2.5 ± 0.7, while the average imaging time for one iMRI was 16.4 min. The intraoperative imaging sequences were T2- and T1-weighted images (contrast, if necessary).

By disease, glioma was determined to be the most common, with 1,711 cases (84.8%), followed by cavernous hemangioma (61 cases; 3.0%), metastatic brain tumor (37 cases; 1.8%), meningioma (31 cases; 1.5%), pituitary adenoma (25 cases; 1.2%), and malignant lymphoma (17 cases; 0.8%). There were 1,110 (64.9%) first cases of gliomas, while there were 601 cases (35.1%) of recurrent gliomas. For these 2,018 patients, subgroups by number of cases, surgical technique, and breakdown of the first occurrence and recurrence by disease are summarized in Table 1. In this study, reoperation and mortality rates were analyzed for 1,704 patients who underwent craniotomy for glioma, as it represented the majority of all cases. In all glioma cases, only one death (0.06%) was reported within 30 days of surgery, wherein the patient underwent a procedure for suspected malignant glioma of the left temporal lobe, which resulted in intratumoral hemorrhage and rapid cerebral edema and death within a few days after tumor biopsy.

Table 1.

Number of cases in the patient subgroup according to disease type

		No. of cases (n = 2,018)	Surgical procedure, n	First/Recurrence
Glioma		1,711 (84.8%)	Craniotomy, 1,704	1110/601
			Open biopsy, 5
			Stereotactic biopsy, 2
WHO grade
	I	43
	II	507
	III	573
	IV	588
Cavernous hemangioma		61 (3.0%)	Craniotomy, 61	61/0
Metastatic brain tumor		37 (1.8%)	Craniotomy, 36 Open biopsy, 1	37/0
Meningioma		31 (1.5%)	Craniotomy, 31	14/17
Pituitary adenoma		25 (1.2%)	TSS, 25	25/0
Malignant lymphoma		17 (0.8%)	Craniotomy, 3 Open biopsy, 10 Stereotactic biopsy, 4	17/0
Other brain diseases		136 (6.7%)	NA	NA

WHO, World Health Organization; TSS, transsphenoidal surgery; NA, not applicable

Meanwhile, there was no case in which re-excision was required at a later date due to insufficient lesion removal.

Unscheduled reoperation within 30 days of surgery was performed in 37 patients (2.2%), due to postoperative bleeding in 17 patients (1.0%), infection in 12 patients (0.7%), hydrocephalus in 6 patients (0.4%), CSF leakage in 1 patient (0.06%), and brain edema in 1 patient (0.06%). Of these cases, reoperation within 24 hours of surgery was performed in 14 cases (0.8%), due to postoperative bleeding in 13 cases (0.8%) and acute hydrocephalus in 1 case (0.06%).

Illustrative cases of aggressive tumor removal with iMRI

For gliomas in particular, multiple MRIs are often performed, and the residual areas on MRI are updated by navigation for more resection. As per our analysis, 64.1% of glioma cases underwent additional resection, a factor that contributed to the high resection rate.

We present illustrative cases of aggressive excision with modality including iMRI. Figure 1 shows an MRI image of a 24-year-old woman with left frontal lobe anaplastic astrocytoma who underwent awake craniotomy (Case 1). After tumor removal, residual tumor was confirmed in front of the removal cavity through the second MRI. After additional resection, the final MRI confirmed no residual tumor; no recurrence was reported 21 years after surgery. We present another case of a 43-year-old woman with right insula-basal ganglia glioblastoma who underwent aggressive tumor removal (Case 2). After resection, the residual tumor was confirmed via MRI; thereafter, we removed any residual tumor as much as possible by making full use of navigation and monitoring. Finally, we were able to achieve a high EOR without paralysis. This case has also been recurrence-free for 17 years after aggressive removal.

Fig. 1.

Two cases of aggressive tumor removal using intraoperative magnetic resonance imaging (iMRI).

Case 1: A case of a 24-year-old woman with left frontal lobe anaplastic astrocytoma who underwent awake craniotomy. After craniotomy, the first T2-weighted MRI showed a left frontal mass (A). After tumor removal, we confirmed residual tumor in front of the removal cavity via a second MRI (B, arrow). After additional resection, the third MRI confirmed no residual tumor (C). This case has been recurrence-free for 21 years after surgery.

Case 2: A case of a 43-year-old woman with right insula-basal ganglia glioblastoma who underwent aggressive tumor removal. After craniotomy, the first the T2-weighted MRI showed high signal in the right insula-basal ganglia (D). After resection, the residual tumor was confirmed via iMRI (E); finally, high extent of resection was achieved after further removal (F). This case was also recurrence-free for 17 years after aggressive removal.

iMRI allows us to deal with unexpected intraoperative complications

Complications such as hemorrhage, brain swelling, and foreign body contamination, which could not have been anticipated via preoperative MRI, were identified in 24 cases (1.4%) and were handled accordingly, thus preventing reoperation at a later date. This included eight cases of epidural and subdural hematoma, six cases of intratumoral hemorrhage, three cases of cerebral swelling, three cases of venous hemorrhage such as sinus, and four other cases.

Cases in which unexpected situations occurred, such as intraoperative hemorrhage, were also detected via iMRI (Figs. 2 and 3). An example is a case of a 65-year-old man with glioblastoma in his left parietal lobe (Case 3). After craniotomy, the first gadolinium-enhanced T1-weighted MRI indicated intratumoral hemorrhage and brain swelling. After tumor and intratumoral hemorrhage removal, we confirmed no residual tumor. Also, another example is a case of astrocytoma in the right parietal lobe of a 20-year-old man (Case 4). After craniotomy, the first MRI demonstrated acute epidural hematoma on the right side. We then properly removed the hematoma and tumor. Even in the rare case of a metal fragment entering the temporal muscle due to a broken drill during surgery, iMRI was able to detect it, wherein it was removed safely (Fig. 3).

Fig. 2.

Two cases in which intraoperative magnetic resonance imaging (iMRI) was able to confirm and deal with unexpected bleeding changes during surgery.

Case 3: A case of a 65-year-old man with glioblastoma in his left parietal lobe. The T1-weighted MRI image before surgery detected a gadolinium-enhanced lesion in his left parietal lobe (A).

After craniotomy, the first gadolinium T1-weighted MRI showed intratumoral hemorrhage and brain swelling (B). After removing the tumor and intratumoral hemorrhage, we confirmed no residual tumor (C).

Case 4: A case of astrocytoma in the right parietal lobe of a 20-year-old man. The GdT1-weighted image showed a cystic tumor in his right parietal lobe before surgery (D). After craniotomy, the first MRI demonstrated acute epidural hematoma on the right side (E, arrow). After removing the hematoma and tumor, we confirmed no residual tumor (arrowhead) and hematoma via a final MRI (F).

Fig. 3.

A case in which a metal fragment was noticed via magnetic resonance imaging (MRI) and was handled accordingly.

The first MRI showed that metal fragments were mixed in due to the breakage of the drill; the fragments could be found in the temporal muscle. We removed them intraoperatively and thus avoided reoperation for foreign body removal.

Discussion

For malignant brain tumors, especially gliomas, high removal rates have been significantly associated with improved prognosis.^1-4) Thus, various devices and techniques, such as navigation systems and iMRI, have been introduced into the operating room to achieve a high EOR. However, it is important not only to accomplish a high EOR but also to minimize complications and avoid neurological deficits using neuromonitoring and awake craniotomy. In 2000, we developed an information-guided surgery that integrates various preoperative and intraoperative information with iMRI as the core in the intelligent operating room, to ensure both the safety and quality of such surgeries.^33,34)

Use of iMRI increases the likelihood of safe and reliable lesion removal in neurosurgery

iMRI has been increasingly recognized as a significant contributor to ensuring the safety of surgery. Resection control is the first benefit of using iMRI for brain surgery, especially brain tumor resection. As per Barbagallo et al., visualization of the brain parenchyma and residual tumor is reliable at the time of initial surgery but is less specific in recurrent cases due to radiation necrosis and artifacts secondary to surgical manipulation. The median resection rate for first gliomas in this present study was 95%, whereas previous data from our institution reported median resection rates of 95%, 95%, and 98% for grade II, III, and IV gliomas, respectively.³⁴⁾ This is characterized by the fact that no residual tumor remained that would have been resected in the preoperative plan. In this present study, we also included 35.1% of recurrent gliomas; however, information-guided surgery, mainly iMRI, allowed the removal of the tumors as per the original strategy. In fact, additional intraoperative resection was performed in 1,097 cases (64.4%); however, no cases required reoperation at a later date for additional resection. Indeed, iMRI is useful not only for the removal of gliomas but also for the removal of vascular tumors, such as cavernous hemangioma. In fact, Torne R et al. reported that iMRI is a safe intraoperative imaging tool in cavernous hemangioma surgery, as it reduces the risk of lesion remnant and is particularly useful for eloquent area lesions, cases with significant brain shift, and large cavernous hemangioma.⁷⁾ Tuleasca et al. have also reported the usefulness of iMRI in combination with awake surgery, especially in eloquent areas.⁸⁾ In this study, all patients underwent craniectomy for cavernous hemangioma, and safe removal was achieved in all cases.

Moreover, updated navigation was made possible via iMRI, which minimized the effect of brain shifts.

Intraoperative complication detection and prevention of unexpected reoperations using iMRI

With the use of iMRI, it is now possible to manage the risk brought about by unexpected situations, such as bleeding and brain swelling during surgery. In addition, intraoperative complications such as hemorrhage, brain swelling, or residual foreign body can now be appropriately handled using iMRI. In this study, complications which could not have been predicted preoperatively were identified in 24 (1.4%) patients using iMRI, and these were managed intraoperatively to prevent reoperation at a later date.

In our analysis of glioma cases, only one death (0.06%) within 30 days of surgery was reported, which is much lower than that of previous reports.¹⁸⁾ To the best of our knowledge, there are no previous reports demonstrating a less than 1% mortality rate within 30 days after neurosurgical craniotomy. Dasenbrock et al. reported a 3.2% (371/11,462) mortality rate within 30 days in 11,462 brain tumor surgeries,¹⁸⁾ wherein the main cause was postoperative bleeding, not infections and shunt troubles. Since iMRI was not used in their series, we speculated that one of the reasons for our low postoperative mortality rate is the use of iMRI to respond to unexpected situations, such as intraoperative and postoperative bleeding. This enhances the safety of information-guided surgery centered on iMRI.

Generally, the reoperation rate within 30 days after surgery is used as a factor to determine the quality of surgery, which is commonly at 3.1-17%.^18,22,25-27) We reviewed past literature and summarized the rate of unexpected reoperation after surgery, presence of iMRI, and mortality rate within 30 days after surgery (Table 2). As per our data show, our unexpected reoperation rate within 30 days was at 2.2%, which is lower than that in previous reports. Kwinta et al. reported that 78 (8.91%) of 875 patients underwent emergency surgery after neurosurgical craniotomy, and brain tumor surgery was an independent risk factor for emergency surgery. Abundant blood flow in malignant brain tumors is often identified as the cause of postoperative bleeding.²⁵⁾ In our series, 84.8% of cases involved surgery for gliomas, which may have increased the postoperative bleeding risk as compared to other reports with relatively few glioma surgeries. Despite this, it can be noted there were very few reoperations due to postoperative bleeding. This is thought to be due to the precise tumor removal via iMRI and the navigation system, the detection of unexpected situations during the operation, and appropriate treatment thereafter. For example, if an unexpected hematoma like an intratumoral hemorrhage is detected via iMRI, the hematoma can be removed at the same time, thus contributing to the lower reoperation rate and lower mortality rate within 30 days after surgery.

Table 2.

Summary of postoperative reoperation rate and mortality rate

Author and Year	Details of the disease	Total no. of cases	Use of iMRI	Reoperation within				30-day mortality rate
				1 day	7 days	14 days	30 days
Dasenbrock et al., 201718)	Brain tumor	11,462	-	NA	NA	NA	3.1% (n = 350)	3.2% (n = 371)
Kwinta et al., 201725)	Brain tumor, trauma, CVD	875	-	NA	NA	NA	8.9% (n = 78)	NA
Marini et al., 201226)	Brain, spine	1,006	-	NA	NA	NA	7.3% (n = 73)	NA
Shah et al., 201230)	Brain tumor	42	+	NA	NA	0% (n = 0)	NA	NA
	Brain tumor	103	-	NA	NA	7.8% (n = 8)	NA	NA
McLaughlin et al., 201522)	Tumor, CVD, trauma, shunt	6,912	-	NA	2.6% (n = 183)	NA	NA	NA
Mukerji et al., 201227)	Tumor, CVD, trauma, shunt	410	-	NA	NA	NA	17% (n = 71)	NA
Present study	Brain tumor	1,704	+	0.8% (n = 14)	1.2% (n = 20)	1.4% (n = 24)	2.2% (n = 37)	0.06% (n = 1)

CVD, cerebrovascular disease; NA, not available; iMRI, intraoperative magnetic resonance imaging

Furthermore, there were no cases of reoperation due to residual tumor, which can be a heavy burden on the patient.

Concerns about prolonged surgery time and increased infection rates with iMRI

Increased proportion of surgical site infections and prolonged surgery time have always been the concern when considering surgery using iMRI. In a study by Ahmadi et al., 516 cases of brain tumor surgery using iMRI were prospectively examined for complications, and the results were compared with 610 cases of general brain tumor surgery. It was found that the average operation time was 57 min longer in the iMRI group; however, no significant difference was noted in terms of postoperative bleeding rate or infection rate between the two groups, and no anesthesiologic disorders were reported in the iMRI group.³⁵⁾

In another study by Shah et al. wherein they compared 42 cases with iMRI with 103 cases with conventional craniotomy in the field of pediatric neurosurgery, the operation time was significantly extended in the former, even if they had the same safety and efficacy. They also presented cases in which the residual tumor during surgery was recognized by iMRI and was thereafter removed, thus requiring no reoperation.³⁰⁾ In our experience, the average time required for a single MRI was 16.4 min, although this certainly increased the operative time.

However, we noted lower reoperation rate due to postoperative infection than those in previous reports.^{18,22,25-27,30)} In our study, 138 (6.8%) pediatric patients underwent surgery using iMRI, and safe tumor removal was possible despite the prolonged operation time.

More recently, iMRI has been utilized by other departments in their surgeries, such as bone tumors in orthopedics and liver cancer in gastrointestinal surgery.³⁶⁾ It is also expected that iMRI will be more widely used in other fields.

Overall, based on our experience with over 2,000 brain surgeries, especially 1,704 glioma resections, we can conclude that surgery with iMRI is safe, has a high rate of lesion removal, and is likely to prevent unexpected complications and reoperations.

However, a limitation to this study is that this is a retrospective analysis. Although this analysis examined a large number of cases and demonstrated low rates of postoperative death, intraoperative complications, and early postoperative reoperation associated with the use of iMRI, a comparison between the outcomes of cases conducted with and without iMRI was lacking. Thus, future prospective studies are needed to verify the usefulness of iMRI.

In conclusion, although this validation was limited to 1,704 glioma resections, constituting the majority of over 2,000 neurosurgical cases at a single institution, these results show that information-guided surgery, mainly iMRI, is less likely to miss residual tumor or unexpected bleeding during surgery, can improve EOR, and may reduce unexpected reoperation rates and mortality rate (0.06%). To date, there have been no reports examining early postoperative mortality and reoperation rates using iMRI in a large number of cases. However, it can be concluded that information-guided surgery, centered on iMRI, has the potential to improve the safety of surgical resections, including those of gliomas.

Conflicts of Interest Disclosure

All authors declare no conflicts of interest (COIs) regarding this article, according to the criteria of Japan Neurosurgical Society. Our self-reported registration of our COI status has been submitted to the society.