Efficacy of intraoperative ultrasonography in neurosurgical tumor resection

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  • 1 Department of Neurosurgery, Albany Medical Center, Albany; and
  • 2 Upstate Medical University College of Medicine, Syracuse, New York
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OBJECTIVE

Intraoperative ultrasonography (IOUS) is a widely accessible imaging modality that provides real-time surgical guidance with minimal identified risk or additional operative time. A recent study by the authors found a strong correlation between IOUS and postoperative MRI findings when evaluating the extent of tumor resection, suggesting that IOUS might have significant clinical implications. The objective of this study was to expand on results from the previous study in order to provide more evidence on the usage of IOUS in the determination of gross-total resection (GTR) in both adult and pediatric patients with brain tumors.

METHODS

This study consisted of a retrospective review of adult and pediatric neurosurgical patients who were treated at Albany Medical Center between August 2009 and March 2016 for a tumor of the brain. All patients were treated with IOUS and then underwent postoperative MRI (with and without contrast) within 1 week of surgery.

RESULTS

A total of 260 patients (55% of whom were males) met inclusion criteria for the study (age range 3 months to 84 years). IOUS results showed a strong association with postoperative MRI results (φ = 0.693, p < 0.001) and an 81% intended GTR rate. In cases in which GTR was pursued, 19% had false-negative results. IOUS was able to accurately identify residual tumor in 100% of subtotal resection cases where resection was stopped due to invasion of tumor into eloquent locations. Cases involving gliomas had a 75% intended GTR rate and a 25% false-negative rate. Cases involving metastatic tumors had an 87% intended GTR rate and a 13% false-negative rate. The sensitivity, specificity, negative predictive value, and positive predictive value are reported for IOUS in all included tumor pathologies, glioma cases, and metastatic tumor cases, respectively.

CONCLUSIONS

The use of IOUS may allow for a reliable imaging modality to achieve a more successful GTR of brain tumors in both adult and pediatric neurosurgical patients. When attempting GTR, the authors demonstrated an 81% GTR rate. The authors also report false-negative IOUS results in 19% of attempted GTR cases. The authors support the use of IOUS in both adult and pediatric CNS tumor surgery to improve surgical outcomes. However, further studies are warranted to address existing limitations with its use to further improve its efficacy and better define its role as an intraoperative imaging tool.

ABBREVIATIONS GTR = gross-total resection; IOUS = intraoperative ultrasonography; NPV = negative predictive value; PPV = positive predictive value; STR = subtotal resection.

OBJECTIVE

Intraoperative ultrasonography (IOUS) is a widely accessible imaging modality that provides real-time surgical guidance with minimal identified risk or additional operative time. A recent study by the authors found a strong correlation between IOUS and postoperative MRI findings when evaluating the extent of tumor resection, suggesting that IOUS might have significant clinical implications. The objective of this study was to expand on results from the previous study in order to provide more evidence on the usage of IOUS in the determination of gross-total resection (GTR) in both adult and pediatric patients with brain tumors.

METHODS

This study consisted of a retrospective review of adult and pediatric neurosurgical patients who were treated at Albany Medical Center between August 2009 and March 2016 for a tumor of the brain. All patients were treated with IOUS and then underwent postoperative MRI (with and without contrast) within 1 week of surgery.

RESULTS

A total of 260 patients (55% of whom were males) met inclusion criteria for the study (age range 3 months to 84 years). IOUS results showed a strong association with postoperative MRI results (φ = 0.693, p < 0.001) and an 81% intended GTR rate. In cases in which GTR was pursued, 19% had false-negative results. IOUS was able to accurately identify residual tumor in 100% of subtotal resection cases where resection was stopped due to invasion of tumor into eloquent locations. Cases involving gliomas had a 75% intended GTR rate and a 25% false-negative rate. Cases involving metastatic tumors had an 87% intended GTR rate and a 13% false-negative rate. The sensitivity, specificity, negative predictive value, and positive predictive value are reported for IOUS in all included tumor pathologies, glioma cases, and metastatic tumor cases, respectively.

CONCLUSIONS

The use of IOUS may allow for a reliable imaging modality to achieve a more successful GTR of brain tumors in both adult and pediatric neurosurgical patients. When attempting GTR, the authors demonstrated an 81% GTR rate. The authors also report false-negative IOUS results in 19% of attempted GTR cases. The authors support the use of IOUS in both adult and pediatric CNS tumor surgery to improve surgical outcomes. However, further studies are warranted to address existing limitations with its use to further improve its efficacy and better define its role as an intraoperative imaging tool.

ABBREVIATIONS GTR = gross-total resection; IOUS = intraoperative ultrasonography; NPV = negative predictive value; PPV = positive predictive value; STR = subtotal resection.

It is well established that the extent of tumor resection has significant consequences on the outcome of both adult and pediatric neurosurgical patients.5,8,10,14,15,20 Gross-total resection (GTR), followed by adjuvant chemotherapy and radiation therapy, often provides the most successful outcomes in the management of CNS tumors.2,5,6 The ability to achieve GTR of a primary or secondary tumor relies on the ability of the surgeon to accurately delineate intraoperatively the margins and characteristics of the tumor.2,5 Accurate margin delineation is also essential to avoid imposing further neurological damage, another essential factor that determines outcomes in this patient population.6,7,20

In previous studies, intraoperative ultrasonography (IOUS) has been shown to be a useful intraoperative tool for both tumor localization and evaluating the extent of resection.2,4–7 IOUS provides real-time image guidance, allowing the surgeon to follow and/or plan the progression of tumor excision with accuracy and ease of use.2,4,5,7,15 In comparison with other intraoperative imaging modalities, such as intraoperative MRI (iMRI), intraoperative CT (iCT) scanning, and neuronavigation systems, IOUS has been shown to have advantages in the areas of financial feasibility, ease of use, and availability, in addition to its superior ability to visualize certain characteristics of CNS tumors.1,2,5,12 With these advantages, IOUS has been successfully used to improve the delineation of tumor margins and the extent of tumor resection in both adult and pediatric patient populations as a supplemental imaging modality.2,5,8,19,20,22,23

Our recent study involving 62 pediatric neurosurgical patients under the care of 1 pediatric neurosurgeon at Albany Medical Center provided more evidence on the utility of IOUS in the determination of GTR.18 The results of IOUS were compared with the postoperative MR images, with and without contrast, obtained within 1 week of surgery. In this study, it was demonstrated that IOUS results significantly correlated with postoperative MRI results. The results exemplified a 71% overall GTR rate, an 80% intended GTR rate (excluding cases performed for debulking purposes), and a negative predictive value (NPV) of 86.3% utilizing IOUS.18

This study aims to expand on results from our previous study in order to provide more evidence on the usage of IOUS in the determination of complete tumor resection. We present a larger patient cohort that includes both pediatric and adult patients, to study the efficacy and sensitivity of this technique in comparison with that of postoperative MR images, the current standard of care. We hypothesize that our results will support those of previous studies—IOUS will add an effective tool to aid in real-time decision making, which allows for more accurate and complete tumor resection, thus rendering the best possible outcomes for both pediatric and adult neurosurgical patients.

Methods

This study consisted of a retrospective chart review of both adult and pediatric patients with brain tumors treated in the neurosurgical service at Albany Medical Center in Albany, New York, between August 2009 and March 2016. The Albany Medical Center Committee on Research Involving Human Subjects approved this study. To obtain the list of patients to be included in the study, the neurosurgical service’s billing list was used to identify patients who underwent resection of brain tumors. For each patient included on the list, the operative report, official pathology report, and official first postoperative MRI report were collected from the electronic medical record. Tumor pathologies with very distinct margins were excluded from analysis in an attempt to avoid artificial elevation of results. All data were securely maintained in a central database within the Albany Medical Center throughout the entire study.

All patients underwent IOUS during the resection procedure and postoperative MRI, with and without contrast, within 1 week of surgery. Patient age at the time of surgery, date of procedure, IOUS and MRI findings, tumor pathology results, and tumor locations were collected. IOUS and MRI findings were examined to determine if any residual tumor was left behind during resection. Negative results refer to an absence of residual tumor on either IOUS or postoperative MRI. An Albany Medical Center board-certified radiologist read all postoperative MR images. Follow-up physician office notes and a second postoperative MRI study performed within 3 months of surgery, per Albany Medical Center department policy, were referenced if postoperative MRI results were unclear to ensure the accuracy of reported data. Follow-up physician office notes and the second postoperative MR images were referenced for approximately half of the cases in this study. All statistics were calculated using the online version of MedCalc (www.medcalc.org), Microsoft Excel 2016, and IBM SPSS Statistics for Macintosh (version 24.0, IBM Corp.).

IOUS Technique

The technique used in this study is identical to that used in our previous study,18 adhering to department policy and standard of care. Prior to surgery, all patients underwent preoperative neuronavigational MRI (Philips) with and without contrast to prepare for intraoperative neuronavigation. On arrival to the operating room, each patient was placed in a Mayfield head holder, secured, and positioned appropriately to adequately present the surgical site. Brainlab was used for neuronavigation, and the patient underwent registration accordingly.

A craniotomy was then performed to expose the underlying dura mater. The site was irrigated with sterile saline to facilitate appropriate acoustic transduction, and the sterile ultrasound probe was introduced. Tumor location and margins were confirmed using Brainlab neuronavigation and IOUS. Throughout the procedure, IOUS was used periodically to assess resection progression.

Once the tumor appeared to be completely resected, or resection was pursued to a point of satisfaction, the IOUS probe was reintroduced for a final scan to reassess for residual tumor. If IOUS detected residual tumor, resection was continued until IOUS revealed a negative evaluation.

If residual tumor was detected by IOUS in an eloquent location, the surgeon could either continue the resection until a negative evaluation was reached or elect to leave residual tumor purposefully, revealing a positive evaluation. Residual tumor was intentionally left due to invasion into eloquent areas in 43 patients. This was done to avoid imposing further neurological deficit, as proceeding with tumor excision in these locations was determined to carry too much risk.

IOUS results were interpreted, and the surgical field was manipulated accordingly in real time by the attending neurosurgeon. Interpretation and manipulation were performed by a neurosurgeon attending from Albany Medical Center, Department of Neurosurgery.

To standardize IOUS results throughout the duration of this study, image interpretation was performed exclusively by the attending neurosurgeon performing the case. Ultrasound equipment, ProSound Alpha 5SX or Alpha 7 (Hitachi Aloka Medical, Ltd.), was used for all imaging studies. No independent reviews of IOUS studies were performed, and no images were saved.

Results

A total of 260 patients met the inclusion criteria for the study during the specified time period, including both recurrent (n = 33) and newly diagnosed (n = 227) brain tumors. Patient ages at the time of surgery ranged from 3 months to 84 years, with a mean age of 46 years; 55% of patients were male (n = 142).

The IOUS results showed a strong association with the postoperative MRI results (φ = 0.639, p < 0.001). Sensitivity (50.6%, 95% CI 39.5%–61.6%), specificity (100.0%, 95% CI 97.9%–100.0%), NPV (80.7%, 95% CI 77.1%–83.8%), and positive predictive value (PPV; 100.0%) were calculated for IOUS in comparison with postoperative MRI results, with and without contrast. See Table 1 for the 2 × 2 table used to calculate these parameters.

TABLE 1.

Sensitivity, specificity, NPV, and PPV of IOUS versus postoperative MRI findings

IOUSPostop MRI Findings
No Residual TumorResidual TumorTotal 
No residual tumor17542217
Residual tumor04343
Total17585260

Of the 260 total cases, 175 demonstrated a negative result (i.e., GTR) for residual tumor on both IOUS and postoperative MRI (67%); 43 cases (17%) showed residual tumor on both IOUS and postoperative MRI as a result of subtotal resection (STR) due to tumor invasion of eloquent anatomical locations. IOUS was able to correctly identify residual tumor in all STR cases. Excluding cases of STR, 175 of 217 cases (81%) demonstrated GTR on both IOUS and postoperative MRI. Thus, the intended GTR rate was 81%. Results are further displayed according to tumor pathology (Table 2) and tumor location (Table 3).

TABLE 2.

Tumor pathology according to official pathology reports

Tumor PathologyNo. of PatientsIOUS Finding/MRI Finding*
Anaplastic astrocytoma2N/N = 0 (0), P/P = 2 (100), N/P = 0 (0)
Anaplastic ependymoma3N/N = 1 (33), P/P = 0 (0), N/P = 2 (67)
Anaplastic oligodendroglioma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Anaplastic juvenile pilocytic astrocytoma, high grade2N/N = 2 (100), P/P = 0 (0), N/P = 0 (0)
Astrocytoma, high grade9N/N = 3 (33), P/P = 4 (44), N/P = 2 (22)
Astrocytoma, low grade7N/N = 4 (57), P/P = 1 (14), N/P = 2 (29)
Atypical choroid plexus papilloma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Choroid plexus carcinoma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Combined primitive neuroectodermal tumor & glioblastoma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Ependymoma7N/N = 4 (57), P/P = 3 (43), N/P = 0 (0)
Fibrillary astrocytoma6N/N = 6 (100), P/P = 0 (0), N/P = 0 (0)
Ganglioglioma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Glioblastoma82N/N = 43 (52), P/P = 17 (21), N/P = 22 (27)
Glioma7N/N = 4 (57), P/P = 2 (29), N/P = 1 (14)
Gliosarcoma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Juvenile pilocytic astrocytoma21N/N = 16 (76), P/P = 5 (24), N/P = 0 (0)
Medulloblastoma5N/N = 5 (100), P/P = 0 (0), N/P = 0 (0)
Metastatic tumor86N/N = 67 (78), P/P = 9 (10), N/P = 10 (12)
Mixed glioma3N/N = 3 (100), P/P = 0 (0), N/P = 0 (0)
Myxopapillary ependymoma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Neurocytoma3N/N = 3 (100), P/P = 0 (0), N/P = 0 (0)
Oligoastrocytoma6N/N = 4 (67), P/P = 0 (0), N/P = 2 (33)
Oligodendroglioma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Papillary tumor of pineal gland1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Pilomyxoid astrocytoma1N/N = 0 (0), P/P = 0 (0), N/P = 1 (100)
Pleomorphic xanthoastrocytoma1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)

N = negative; N/N = tumor not present on IOUS or postoperative MRI; N/P = tumor not present on IOUS but present on postoperative MRI; P = positive; P/P = tumor present on IOUS and postoperative MRI.

Presented as the number of patients (%).

TABLE 3.

Tumor location according to the official pathology report

Tumor LocationNo. of PatientsIOUS/MRI (No. [%])
3rd ventricle2N/N = 2 (100), P/P = 0 (0), N/P = 0 (0)
4th ventricle9N/N = 6 (67), P/P = 3 (33), N/P = 0 (0)
Anterior cranial fossa2N/N = 0 (0), P/P = 2 (100), N/P = 0 (0)
Cerebellum21N/N = 16 (76), P/P = 1 (5), N/P = 4 (19)
Frontal87N/N = 64 (74), P/P = 10 (11), N/P = 13 (15)
Frontoparietal8N/N = 4 (50), P/P = 1 (13), N/P = 3 (37)
Frontotemporal2N/N = 1 (50), P/P = 1 (50), N/P = 0 (0)
Insula1N/N = 0 (0), P/P = 1 (100), N/P = 0 (0)
Intraventricular6N/N = 5 (83), P/P = 1 (17), N/P = 0 (0)
Midbrain1N/N = 0 (0), P/P = 1 (100), N/P = 0 (0)
Middle cranial fossa1N/N = 0 (0), P/P = 1 (100), N/P = 0 (0)
Occipital20N/N = 13 (65), P/P = 2 (10), N/P = 5 (25)
Parafalcine1N/N = 1 (100), P/P = 0 (0), N/P = 0 (0)
Parietal29N/N = 23 (79), P/P = 5 (17), N/P = 1 (3)
Parietooccipital16N/N = 11 (69), P/P = 0 (0), N/P = 5 (31)
Posterior cranial fossa5N/N = 5 (100), P/P = 0 (0), N/P = 0 (0)
Temporal43N/N = 19 (44), P/P = 14 (33), N/P = 10 (23)
Temporoparietal3N/N = 3 (100), P/P = 0 (0), N/P = 0 (0)
Thalamus3N/N = 2 (67), P/P = 0 (0), N/P = 1 (33)

Of the 260 cases, 42 (16%) had false-negative results with IOUS. Excluding cases of STR, 42 of 217 patients had a false-negative result with IOUS (19%). Of these 42 cases, 30 (71%) were gliomas, 10 (24%) were metastatic neoplasms, and 2 (5%) were anaplastic ependymomas. Thirty-three cases (79%) included newly diagnosed tumors, and no predominance to right or left hemisphere was observed (right hemisphere tumors occurred in 50% of cases, n = 21). Thirteen tumors (31%) involved the frontal lobes, and 10 (24%) involved the temporal lobes. Patient ages ranged from 2 to 82 years, with a mean age of 50 years. See Tables 4 and 5 for IOUS false-negative results displayed according to tumor pathology (Table 4) and tumor location (Table 5) according to the official pathology report.

TABLE 4.

False-negative results based on tumor pathology according to official pathology report

Tumor PathologyNo. of FNRs (%)Case Percentage*Total No. of Cases
Anaplastic ependymoma2 (5)67%3
Astrocytoma, high grade2 (5)22%9
Astrocytoma, low grade2 (5)29%7
Glioblastoma22 (52)27%82
Glioma, low grade1 (2)14%7
Metastatic tumor (various origins)10 (24)12%86
Oligoastrocytoma2 (5)33%6
Pilomyxoid astrocytoma1 (2)100%1

FNR = false-negative result (N/P).

The percentage of false negatives for each individual tumor pathology.

TABLE 5.

False-negative results based on tumor location according to official pathology report

Tumor LocationNo. of FNRs (%)Case PercentageTotal No. of Cases
Cerebellum4 (10)19%21
Frontal13 (31)15%87
Frontoparietal3 (7)37%8
Occipital5 (12)25%20
Parietal1 (2)3%29
Parietooccipital5 (12)31%16
Temporal10 (24)23%43
Thalamus1 (2)25%4

Of the 33 reported recurrent tumors included in the study, 9 showed a false-negative result with IOUS (27%). Of these false-negative results, 2 were astrocytomas (low grade, 22%), 3 were glioblastomas (33%), and 2 were oligoastrocytomas (22%). In terms of recurrent tumor location, 3 tumors were within the parietooccipital lobes (33%) and 3 were within the temporal lobes (33%). All cases of recurrent tumors reported prior excision, chemotherapy, and radiation treatment.

An independent analysis of gliomas (n = 152) and metastatic neoplasms (n = 86) was also completed. IOUS results during glioma resection correlated with postoperative MRI results (φ = 0.618, p < 0.001). IOUS in glioma resection was found to have a sensitivity of 50.8% (95% CI 37.7%–63.9%), a specificity of 100% (95% CI 96.0%–100.0%), an NPV of 75.2% (70.2%–79.7%), and a PPV of 100.0% in comparison with postoperative MRI findings. Ninety-one of 152 glioma cases resulted in GTR, 31 resulted in STR, and 30 yielded false-negative results. Excluding STRs, GTR was achieved in 91 of 121 cases (75%) and false-negative results were identified in 30 of 121 cases (25%). Of the 30 false-negative results, 22 were glioblastomas (73%) and 5 were astrocytomas of various grades (17%). IOUS was able to correctly identify residual tumor in all glioma cases where STR was desired.

IOUS results during metastatic tumor resection correlated with postoperative MRI results as well (φ = 0.642, p < 0.001). IOUS in metastatic tumor resection was found to have a sensitivity of 47.4% (95% CI 24.5%–71.1%), a specificity of 100% (95% CI 94.6%–100.0%), an NPV of 87.0% (95% CI 81.4%–91.1%), and a PPV of 100% in comparison with postoperative MRI. Sixty-seven of 86 metastatic tumor cases resulted in GTR, 9 resulted in STR, and 10 yielded false-negative results. Excluding STRs, GTR was achieved in 67 of 77 cases (87%), and false-negative results were identified in 10 of 77 cases (13%). IOUS was able to correctly identify residual tumor in all metastatic tumor cases in which STR had been desired. Results for glioma and metastatic tumor analyses are summarized in Table 6.

TABLE 6.

Glioma and metastatic tumor IOUS results

VariableGlioma (n = 152)Metastatic Tumors (n = 86)
Association, φ0.618 (p <0.001)0.642 (p <0.001)
Sensitivity50.8% (37.7–63.9%)47.4% (24.5–71.1%)
Specificity100.0% (96.0–100.0%)100.0% (94.6–100%)
NPV75.2% (70.2–79.7%)87.0% (81.4–91.1%)
PPV100.0%100.0%
STR31 (20%)9 (10%)
GTR rate*75%87%
False-negative rate*25%13%

Association = association between IOUS and postoperative MRI results.

These rates exclude STR cases where GTR was electively decided against intraoperatively.

The proportion of false negatives for gliomas (25%) was found to be higher than that of metastatic neoplasms (13%; p = 0.041). An association between IOUS and postoperative MRI results in these groups showed no statistically significant difference (p = 0.770).

Discussion

Refining surgical techniques to improve the safe resection of CNS tumors may have significant clinical implications in both pediatric and adult neurosurgical patients. Despite recent advancements,9 the estimated 5-year survival rate for malignant brain neoplasms remains at 34%. The most common primary malignancy of the brain, glioblastoma, retains a 5-year survival rate of 5%.11 Further improvements in the management of these malignancies are warranted. In this regard, real-time intraoperative imaging technologies have shown utility in providing assistance to resection in a dynamic surgical field. Increasing attention has been paid to IOUS technologies, with IOUS being reported as a widely accessible, financially feasible, and reliable imaging modality to follow and modify the surgical plan in real time. Our study provides a retrospective cohort analysis of the efficacy of IOUS in brain tumor resection. Our results might support previously reported findings on the practicality and efficacy of IOUS, while also supporting current limitations to its use.

With the use of IOUS as an adjunctive imaging modality to guide tumor resection, we report an intended GTR rate of 81% across the diverse cases included in our study. IOUS interpretations showed a strong association with postoperative MRI results (φ = 0.639, p < 0.001) and a respectable NPV of 80.7%. Of the 43 included STRs, IOUS was able to correctly identify residual tumor in 100% of cases. IOUS provided useful intraoperative information, allowing the surgeon to visualize the extent of residual tumor when making the decision to proceed or conclude the resection based on the benefit/risk ratio. In all cases, IOUS allowed for real-time imaging of the resection cavity margin, residual tumor, and surrounding brain parenchyma and vasculature to assess the progression of resection while allowing for modification of the intraoperative plan as necessary. Previous studies have reported similar findings on the efficacy and benefits associated with using IOUS to aid in the resection of CNS tumors.5,8,18–21,23

Of note, we have reported false-negative IOUS interpretations in 42 cases (19%) in which GTR was sought (excludes STRs). Thirty cases involved gliomas of varying grades (71%), 22 of which were glioblastomas (52%) and 10 involved metastatic tumors (24%). Nine cases (21%) were recurrent tumors that had previously been treated with resection, chemotherapy, and radiotherapy. It has been reported that the true benefit of IOUS lies with its ability to assess for residual tumor intraoperatively in efforts to increase the extent of resection.9 Rather than discounting the utility of IOUS, we suggest that this result might further elucidate limitations in its use that negatively impact image resolution. These limitations may have influenced the false-negative rate in our study. Discussion of improving these limitations is warranted.

Studies by Woydt et al. and Rygh et al. showed that IOUS is able to accurately identify thick rims of hyperechoic residual tumor along the resection cavity margin with a 100% PPV, but thin rims of hyperechoic residual tumor may be detected with less accuracy.16,24 This inaccuracy may be attributed to infiltrating tumor tissue masked by enhancement artifacts caused by tissue debris, microscopic air pockets, and blood products that accumulate progressively throughout the resection. The presence of these artifacts might prevent surgeons from correctly identifying residual tumor tissue.9

To improve GTR rates in our patients, optimal IOUS image resolution must be maintained to provide accurate data for optimizing resections and maximizing safety. To minimize enhancement artifact, Selbekk et al.17 reported that inserting smaller, phased-array ultrasound probes into the resection cavity, with care taken not to cause mechanical injury, may reduce imaging artifact by reducing the distance between the transducer and the cavity floor. Common practice is to introduce the probe superficially. Increased distance between the transducer and the resection margin dampens the ultrasound pulse and increases brightness artifact due to the differences in attenuation between brain parenchyma and saline introduced into the resection cavity as part of IOUS protocol.17 This brightness artifact might cause inaccurate interpretation of resection success, resulting in residual tumor.9,17 A drawback of decreasing distance is decreasing the width of the ultrasound image. Scanning the resection cavity or examining specific tissue locations where residual tumor is suspected may minimize this limitation.17 To further reduce this problem, further exploration into alternatives to saline for IOUS imaging could prove useful. A fluid with acoustic properties closer to those of brain tissue might reduce brightness artifact and allow for a more accurate IOUS image.

Additionally, the ability to acquire a high-quality IOUS image is highly user dependent. Common criticisms of IOUS imaging are the perception of poor-quality imaging and poor orientation to surrounding anatomy. Obtaining a quality IOUS image in a dynamic resection cavity impacted by tissue adaptations and brain shift requires sufficient practice and experience. To obtain high-quality images, the surgeon must be well rehearsed in the proper technique of ultrasonography and the appearance of intracranial anatomy and malignancy. While some institutions offer a radiologist’s interpretation intraoperatively, this is not possible for many due to logistical reasons. This is the case at our institution, where IOUS interpretation was done exclusively by the attending neurosurgeon. Increases in exposure to IOUS in residency training and daily practice may improve perceived IOUS utility, as experience can be quickly gained. Additionally, images can be coregistered with preoperative MR images to provide improved intracranial orientation, enhancing ease of use.9

The results of independent analyses of included gliomas and metastatic tumors are provided in Table 6. The high rate of glioma false negatives might be attributed to several factors. The majority of these false-negative results were for highly invasive tumor pathologies (73% were glioblastomas and 17% were astrocytomas). These results coincide with those recently reported by Coburger et al., who prospectively compared histopathological results and intraoperative MRI, 5-aminolevulinic acid (5-ALA), and IOUS findings in 33 glioblastoma cases.3 All 3 imaging techniques provided false-negative results in 90% of cases. For IOUS specifically, 93% of negative results were false negatives. Of these, 64% contained solid tumor and 29% had tumor invasion into the normal neural tissue. This demonstrates the invasive nature of glioblastomas. In their case series, Unsgaard et al. demonstrated similar findings on the reduced imaging accuracy of glioblastomas, reporting that the PPV of IOUS was the lowest for glioblastoma (79%) compared with low-grade glioma and metastases (100%).22 Interestingly, the same group reported significantly increased accuracy in IOUS-guided resection of glioblastomas after the team acquired experience with IOUS over time.16 This may further support the concept of user dependency in IOUS.

Metastatic tumors often have well-demarcated borders with the surrounding brain parenchyma,22 making en bloc resection with positive outcomes a common goal in these cases. They often appear hyperechoic and homogeneous with well-defined borders on IOUS. For this reason, identification of these lesions using IOUS prior to resection is done with ease. Difficulties come with resection progression, where it may become difficult to differentiate residual tumor from normal tissue due to imaging artifact, as previously discussed.13 In addition, certain metastatic lesions necessitated removal of the lesion in a piecemeal fashion, due to either difficulty in defining the tumor margin or tumor vascularity. The elevated incidence of metastatic tumor false-negative results reported in our study may thus be due to the same IOUS limitations that can be generalized to many other tumor pathologies. Additionally, this elevated incidence may be due to the large number of metastatic tumor cases included in this study. Eighty-six of the 260 (33%) surgical cases included in this study involved metastatic tumors, 67 of which (87%) resulted in GTR. Metastatic tumors resulted in a significantly smaller proportion of false-negative results in comparison with gliomas (p = 0.041). This finding coincides with previously reported data that metastatic tumor margins, often clearly marginalized, are visualized well with IOUS.4,5,14,21,22

Conclusions

The use of IOUS might help achieve a more successful GTR in both adult and pediatric neurosurgical patients. When attempting GTR, we demonstrated an 81% GTR rate. We also reported false-negative IOUS results in 19% of attempted GTR cases. We support the use of IOUS in both adult and pediatric CNS tumor surgery to improve surgical outcomes. However, further studies are warranted to address existing limitations with its use to further improve its efficacy and better define its role as an intraoperative imaging tool.

To reach additional success in achieving GTR, we might consider utilizing IOUS alongside other intraoperative imaging modalities, such as intraoperative fluorescence imaging, especially in high-grade gliomas. Intraoperative fluorescence imaging is being increasingly used in our practice, providing successful visualization of neoplastic tissues in real time. It might be useful to study the combined efficacy of IOUS and intraoperative fluorescence imaging in achieving a higher GTR rate in invasive CNS tumor cases. Additionally, it might be useful to perform a subsequent study on the efficacy of IOUS in our institution after attempting to increase its utilization and familiarity within our faculty.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Adamo. Acquisition of data: Adamo, Smith, Perloff. Analysis and interpretation of data: Adamo, Sweeney, Taplin. Drafting the article: Sweeney. Critically revising the article: Adamo. Reviewed submitted version of manuscript: Adamo, Sweeney. Approved the final version of the manuscript on behalf of all authors: Adamo. Statistical analysis: Sweeney, Smith. Study supervision: Adamo, Taplin.

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    • Export Citation
  • 4

    Enzmann DR, Wheat R, Marshall WH, Bird R, Murphy-Irwin K, Karbon K, : Tumors of the central nervous system studied by computed tomography and ultrasound. Radiology 154:393399, 1985

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Hammoud MA, Ligon BL, elSouki R, Shi WM, Schomer DF, Sawaya R: Use of intraoperative ultrasound for localizing tumors and determining the extent of resection: a comparative study with magnetic resonance imaging. J Neurosurg 84:737741, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    LeRoux PD, Berger MS, Ojemann GA, Wang K, Mack LA: Correlation of intraoperative ultrasound tumor volumes and margins with preoperative computerized tomography scans. An intraoperative method to enhance tumor resection. J Neurosurg 71:691698, 1989

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Mair R, Heald J, Poeata I, Ivanov M: A practical grading system of ultrasonographic visibility for intracerebral lesions. Acta Neurochir (Wien) 155:22932298, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Mari AR, Shah I, Imran M, Ashraf J: Role of intraoperative ultrasound in achieving complete resection of intra-axial solid brain tumours. J Pak Med Assoc 64:13431347, 2014

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Moiyadi AV: Intraoperative ultrasound technology in neuro-oncology practice—current role and future applications. World Neurosurg 93:8193, 2016

  • 10

    Neidert MC, Hostettler IC, Burkhardt JK, Mohme M, Held U, Kofmehl R, : The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma. Neurosurg Rev 39:401409, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, : CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol 17 (Suppl 4):iv1iv62, 2015

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Petridis AK, Anokhin M, Vavruska J, Mahvash M, Scholz M: The value of intraoperative sonography in low grade glioma surgery. Clin Neurol Neurosurg 131:6468, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Picarelli H, de Lima Oliveira M, Bor-Seng-Shu E, Ribas ES, Santos AM, Teixeira MJ: Intraoperative ultrasonography for presumed brain metastases: a case series study. Arq Neuropsiquiatr 70:793798, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Renner C, Lindner D, Schneider JP, Meixensberger J: Evaluation of intra-operative ultrasound imaging in brain tumor resection: a prospective study. Neurol Res 27:351357, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Roth J, Biyani N, Beni-Adani L, Constantini S: Real-time neuronavigation with high-quality 3D ultrasound SonoWand in pediatric neurosurgery. Pediatr Neurosurg 43:185191, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Rygh OM, Selbekk T, Torp SH, Lydersen S, Hernes TAN, Unsgaard G: Comparison of navigated 3D ultrasound findings with histopathology in subsequent phases of glioblastoma resection. Acta Neurochir (Wien) 150:10331042, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Selbekk T, Jakola AS, Solheim O, Johansen TF, Lindseth F, Reinertsen I, : Ultrasound imaging in neurosurgery: approaches to minimize surgically induced image artefacts for improved resection control. Acta Neurochir (Wien) 155:973980, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Smith H, Taplin A, Syed S, Adamo MA: Correlation between intraoperative ultrasound and postoperative MRI in pediatric tumor surgery. J Neurosurg Pediatr 18:578584, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Tian YJ, Lin S, Liu HZ, Wang LS, He W, Zhang MZ, : [Value of intra-operative ultrasound in detecting the boundaries of intra cranial gliomas.] Zhonghua Yi Xue Za Zhi 89:13051308, 2009 (Chinese)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Ulrich NH, Burkhardt JK, Serra C, Bernays RL, Bozinov O: Resection of pediatric intracerebral tumors with the aid of intraoperative real-time 3-D ultrasound. Childs Nerv Syst 28:101109, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Unsgaard G, Ommedal S, Muller T, Gronningsaeter A, Nagelhus Hernes TA: Neuronavigation by intraoperative three-dimensional ultrasound: initial experience during brain tumor resection. Neurosurgery 50:804812, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Unsgaard G, Selbekk T, Brostrup Müller T, Ommedal S, Torp SH, Myhr G, : Ability of navigated 3D ultrasound to delineate gliomas and metastases—comparison of image interpretations with histopathology. Acta Neurochir (Wien) 147:12591269, 2005

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Wang J, Liu X, Ba YM, Yang YL, Gao GD, Wang L, : Effect of sonographically guided cerebral glioma surgery on survival time. J Ultrasound Med 31:757762, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Woydt M, Krone A, Becker G, Schmidt K, Roggendorf W, Roosen K: Correlation of intra-operative ultrasound with histopathologic findings after tumour resection in supratentorial gliomas. A method to improve gross total tumour resection. Acta Neurochir (Wien) 138:13911398, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

If the inline PDF is not rendering correctly, you can download the PDF file here.

Contributor Notes

Correspondence Matthew A. Adamo: AMC Neurosurgery Group, Albany, NY. adamom@mail.amc.edu.

INCLUDE WHEN CITING Published online February 16, 2018; DOI: 10.3171/2017.11.PEDS17473.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

  • 1

    Auer LM, van Velthoven V: Intraoperative ultrasound (US) imaging. Comparison of pathomorphological findings in US and CT. Acta Neurochir (Wien) 104:8495, 1990

  • 2

    Chacko AG, Kumar NK, Chacko G, Athyal R, Rajshekhar V: Intraoperative ultrasound in determining the extent of resection of parenchymal brain tumours—a comparative study with computed tomography and histopathology. Acta Neurochir (Wien) 145:743748, 2003

    • Crossref
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  • 3

    Coburger J, Scheuerle A, Pala A, Thal D, Wirtz CR, Konig R: Histopathological insights on imaging results of intraoperative magnetic resonance imaging, 5-aminolevulinic acid, and intraoperative ultrasound in glioblastoma surgery. Neurosurgery 81:165174, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Enzmann DR, Wheat R, Marshall WH, Bird R, Murphy-Irwin K, Karbon K, : Tumors of the central nervous system studied by computed tomography and ultrasound. Radiology 154:393399, 1985

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Hammoud MA, Ligon BL, elSouki R, Shi WM, Schomer DF, Sawaya R: Use of intraoperative ultrasound for localizing tumors and determining the extent of resection: a comparative study with magnetic resonance imaging. J Neurosurg 84:737741, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    LeRoux PD, Berger MS, Ojemann GA, Wang K, Mack LA: Correlation of intraoperative ultrasound tumor volumes and margins with preoperative computerized tomography scans. An intraoperative method to enhance tumor resection. J Neurosurg 71:691698, 1989

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Mair R, Heald J, Poeata I, Ivanov M: A practical grading system of ultrasonographic visibility for intracerebral lesions. Acta Neurochir (Wien) 155:22932298, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Mari AR, Shah I, Imran M, Ashraf J: Role of intraoperative ultrasound in achieving complete resection of intra-axial solid brain tumours. J Pak Med Assoc 64:13431347, 2014

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Moiyadi AV: Intraoperative ultrasound technology in neuro-oncology practice—current role and future applications. World Neurosurg 93:8193, 2016

  • 10

    Neidert MC, Hostettler IC, Burkhardt JK, Mohme M, Held U, Kofmehl R, : The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma. Neurosurg Rev 39:401409, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, : CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol 17 (Suppl 4):iv1iv62, 2015

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Petridis AK, Anokhin M, Vavruska J, Mahvash M, Scholz M: The value of intraoperative sonography in low grade glioma surgery. Clin Neurol Neurosurg 131:6468, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Picarelli H, de Lima Oliveira M, Bor-Seng-Shu E, Ribas ES, Santos AM, Teixeira MJ: Intraoperative ultrasonography for presumed brain metastases: a case series study. Arq Neuropsiquiatr 70:793798, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Renner C, Lindner D, Schneider JP, Meixensberger J: Evaluation of intra-operative ultrasound imaging in brain tumor resection: a prospective study. Neurol Res 27:351357, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Roth J, Biyani N, Beni-Adani L, Constantini S: Real-time neuronavigation with high-quality 3D ultrasound SonoWand in pediatric neurosurgery. Pediatr Neurosurg 43:185191, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Rygh OM, Selbekk T, Torp SH, Lydersen S, Hernes TAN, Unsgaard G: Comparison of navigated 3D ultrasound findings with histopathology in subsequent phases of glioblastoma resection. Acta Neurochir (Wien) 150:10331042, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Selbekk T, Jakola AS, Solheim O, Johansen TF, Lindseth F, Reinertsen I, : Ultrasound imaging in neurosurgery: approaches to minimize surgically induced image artefacts for improved resection control. Acta Neurochir (Wien) 155:973980, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Smith H, Taplin A, Syed S, Adamo MA: Correlation between intraoperative ultrasound and postoperative MRI in pediatric tumor surgery. J Neurosurg Pediatr 18:578584, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Tian YJ, Lin S, Liu HZ, Wang LS, He W, Zhang MZ, : [Value of intra-operative ultrasound in detecting the boundaries of intra cranial gliomas.] Zhonghua Yi Xue Za Zhi 89:13051308, 2009 (Chinese)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Ulrich NH, Burkhardt JK, Serra C, Bernays RL, Bozinov O: Resection of pediatric intracerebral tumors with the aid of intraoperative real-time 3-D ultrasound. Childs Nerv Syst 28:101109, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Unsgaard G, Ommedal S, Muller T, Gronningsaeter A, Nagelhus Hernes TA: Neuronavigation by intraoperative three-dimensional ultrasound: initial experience during brain tumor resection. Neurosurgery 50:804812, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Unsgaard G, Selbekk T, Brostrup Müller T, Ommedal S, Torp SH, Myhr G, : Ability of navigated 3D ultrasound to delineate gliomas and metastases—comparison of image interpretations with histopathology. Acta Neurochir (Wien) 147:12591269, 2005

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Wang J, Liu X, Ba YM, Yang YL, Gao GD, Wang L, : Effect of sonographically guided cerebral glioma surgery on survival time. J Ultrasound Med 31:757762, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Woydt M, Krone A, Becker G, Schmidt K, Roggendorf W, Roosen K: Correlation of intra-operative ultrasound with histopathologic findings after tumour resection in supratentorial gliomas. A method to improve gross total tumour resection. Acta Neurochir (Wien) 138:13911398, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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