• Users Online: 18
  • Print this page
  • Email this page


 
 
Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 132-144

Intraoperative imaging in the management of brain tumors: A review of contemporary adjuncts used in routine practice


1 Department of Surgical Oncology, Neurosurgical Oncology Services, Tata Memorial Centre; Homi Bhabha National Institute, Health Sciences Section, Mumbai, Maharashtra, India
2 Department of Neurosurgery, University Hospital of Coventry and Warwickshire, Coventry, United Kingdom

Date of Web Publication02-Nov-2021

Correspondence Address:
Dr. Aliasgar V Moiyadi
Tata Memorial Centre, Mumbai - 400 012, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJNO.IJNO_419_21

Rights and Permissions
  Abstract 


Optimizing the extent of resection remains a primary goal of surgery for diffuse gliomas and most brain tumors. Limitations of capabilities of human visualization necessitate the use of adjuncts to augment and improve outcomes. This review serves to encapsulate the commonly used adjuncts in neurosurgical oncology. There exists a plethora of such techniques which can broadly be divided into image-guided techniques (including navigation and real-time intraoperative imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging) as well as optical imaging techniques (of which fluorescence is the most widely used one). This review describes these techniques briefly and reviews pertinent literature focusing on the utility and benefits of these modalities. Both diagnostic accuracy and the therapeutic outcomes are discussed. Although each modality is supported by published literature, the quality of the evidence is variable. It is difficult to make comparisons across studies due to variability in study design, populations included, and the techniques used for the assessment of outcomes. It is likely that a combination of modalities will be synergistic and judicious use of the range of adjuncts is advisable.

Keywords: Fluorescence, intraoperative, magnetic resonance imaging, review, ultrasound


How to cite this article:
Moiyadi AV, Shaikh ST. Intraoperative imaging in the management of brain tumors: A review of contemporary adjuncts used in routine practice. Int J Neurooncol 2021;4, Suppl S1:132-44

How to cite this URL:
Moiyadi AV, Shaikh ST. Intraoperative imaging in the management of brain tumors: A review of contemporary adjuncts used in routine practice. Int J Neurooncol [serial online] 2021 [cited 2021 Dec 5];4, Suppl S1:132-44. Available from: https://www.Internationaljneurooncology.com/text.asp?2021/4/3/132/329814




  Introduction Top


It is now unanimously agreed and well documented in literature that the extent of resection for gliomas (both high-grade gliomas [HGG]; as well as low-grade gliomas [LGG]), which constitute the most common type of brain tumors, is a key prognostic marker in terms of outcome. Due to their infiltrative growth pattern, with tumors merging imperceptibly into native brain parenchyma, gross total resection (GTR) is difficult, a challenge compounded manifold by close proximity to eloquent substrates. The complex three-dimensional (3D) structure and intraoperative deformation of the brain further poses unique challenges during neurosurgical procedures, very often leading to significant discordance between the subjectively estimated extent of resection and the true objectively assessed extent.[1] Most of these “misses” are due to inadequate intraoperative visualization of tumor residue. Therefore, augmentation of this visualization is invaluable when dealing with such tumors. Moreover, unintended damage to eloquent substrates can be minimized or completely avoided. Intraoperative image guidance modalities assist in planning the surgical approach, localization of the disease in relation to adjacent eloquent regions and offer accurate resection control in brain tumors.

The well-established adjuncts can be broadly categorized into image-guided surgery (IGS) techniques, enhanced optical imaging (OI), and visualization techniques and intraoperative neuromonitoring adjuncts. Whereas the first two comprise techniques that facilitate extended resections by the demonstration of the tumor extent, neuromonitoring (awake as well as under anesthesia) is indispensable for ensuring function preservation.

This review will focus on the former category (IGS and OI tools) as applied to neuro-oncological surgeries. IGS includes neuronavigation (NN) (static, preoperative imaging-based) as well as real-time intraoperative imaging tools such as intraoperative ultrasound (IUS), intraoperative magnetic resonance imaging (IMRI), and intraoperative computed tomography (ICT). Fluorescence-guided surgery (FGS) will encompass the use of either 5-aminolevulinic acid (5-ALA) or sodium fluorescein (SF). The scope of this review article includes a broad description of the various established intraoperative adjuncts outlining their mechanism of action and application in neuro-oncological surgeries, advantages and disadvantages, as well as a review of available literature as regard to their role. We will restrict our review to established techniques touching upon newer developments as related to these techniques.


  Methodology Top


A PubMed search was performed by adjusting filters for articles in the English language from 2001 onward. We chose to selectively include studies which were either meta-analysis and/or systematic reviews or large clinical studies with/without reviews. MESH terms searched for were neurosurgery, brain tumor, glioma, intraoperative, resection, ultrasound, navigation, fluorescence, magnetic resonance imaging (MRI), computed tomography, and imaging. Boolean operators used were AND and OR variably. Studies of spinal tumors/pathologies and articles focusing on neuromonitoring were excluded from the results. The authors reviewed the studies and identified significant meta-analysis and systematic reviews for each modality and the results were tabulated [Table 1].[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] Further, for each of the individual modalities, major studies published during this time period were screened and identified. Cross references were checked to identify key studies. They were categorized into studies evaluating the role of these adjuncts as diagnostic agents (diagnostic accuracy with histopathology [and IMRI in some series] as gold standard variably) [Table 2][20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34] as well as studies assessing therapeutic outcomes (in terms of extent of resection with postoperative MRI as gold standard and survival) [Table 3].[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52] Being imaging tools, the diagnostic accuracy is a key outcome parameter, and yet, by virtue of the effect of the imaging tool on the resection outcomes, survival may be potentially influenced. Hence, a dual assessment was thought to be important. To assess the level of evidence, the AANS guidelines for studies of diagnostic accuracy and therapeutic efficacy were followed.[53],[54] As this was not a systematic review, the authors selected the studies on a thorough review and assessment of key studies based on their personal experience.
Table 1: Summary of important systematic reviews and meta-analyses published

Click here to view
Table 2: Summary of major studies of diagnostic accuracy (histopathology or intraoperative magnetic resonance as gold standard)

Click here to view
Table 3: Summary of major studies assessing the therapeutic efficacy of various modalities (using postoperative magnetic resonance as gold standard for resection control estimation)

Click here to view


Image guided surgery

IGS is omnipresent in neurosurgical operating theaters. IGS utilizes radiological images acquired either preoperatively (”static” NN) or in real-time intraoperatively.

Neuronavigation

This has been one of the most widely used adjuncts in neurosurgery. NN provides “static images” much like standard directional GPS/navigational aids. This helps in planning craniotomy, to identify location of known anatomical landmarks and tumors [Figure 1], and can be particularly useful for biopsies of deep seated/small lesions. However, due to the phenomenon of brain shift, leading to inaccuracies in image registration, its role in resection control for tumors is equivocal at best. Two retrospective studies showed a benefit of NN alone (31% vs. 19% GTR; 64% vs. 38% GTR) in gliomas,[49],[50] whereas a single randomized controlled trial (RCT) showed no such benefit.[51] Diffusion tensor imaging (DTI)-based navigation may be superior to routine NN as evidenced by the findings of a RCT of 238 patients by Wu et al.[52] They found that, in HGG, GTR was much higher (74.4% vs. 33.3%), and postoperative motor deterioration was much lower in DTI navigation group (15.3% vs. 32.8%).
Figure 1: Screenshots from the navigation screen showing a left frontal glioma operated under awake conditions. (a) The relation of the tumor with the various white matter tracts is clearly visible. This can be rotated “virtually” to provide a 360° view while planning the surgery. (b) The navigation helps delineate the tumor boundaries and eloquent substrates, thereby allowing appropriate placement of the craniotomy

Click here to view


Despite its widespread use, NN by itself is of limited value in the resection control of tumors, where updated (and often repeated) images are necessary. The most widely used forms of intraoperative imaging in neurological surgery are IMRI and IUS and will be reviewed further. ICT is less useful in the context of brain tumors. [Table 4] compares these various types of intraoperative imaging techniques.
Table 4: Comparison of intra-operative radiological imaging techniques[55]

Click here to view


Intraoperative magnetic resonance imaging

This was first described close to 30 years ago. The early systems were ultra-low field in strength (0.2 T) subsequently progressing to low field (0.5 T) and high field strengths (>1.5T). IMRI overcomes the fallacy of brain shift which can occur once resection is commenced. IMRI has shown to improve the extent of resection in HGG as well as LGG.[13],[14] Given its superior tissue resolution and image quality, IMRI remains the gold standard imaging modality for brain tumors. However, as interobserver variation exists in the interpretation of the residual tumor (though this is much less than for ultrasound), it has been difficult to establish a causal relationship between the use of IMRI and improvement in the extent of resection. So far, three RCTs have been conducted to study its role. A recent meta-analysis studied the RCTs and 12 observational studies and concluded that IMRI leads to a statistically significant improvement in extent of resection in LGG but not for HGG.[14] In terms of therapeutic benefit, although a RCT performed in 2011 by Senft et al.,[46] found a longer progression-free survival (PFS) with IMRI (218 vs. 110 days without IMRI), the meta-analysis found that there was no significant improvement in the PFS or overall survival (OS).[14] Considering the huge logistical challenges in setting up an IMRI and the complexities of acquiring repeated intraoperative magnetic resonance scans, it has not found widespread application, as would have been expected. Besides, cost-effectiveness issues need to be addressed. Multipurpose (two room) IMRI solutions would seem to be more cost effective and less resource draining than dedicated IMRI systems. Miniaturization and development of portable solutions are likely to increase the acceptability of IMRI.

Intraoperative ultrasound

B-mode gray scale ultrasound imaging is one of the oldest diagnostic imaging modalities used in medicine. It was also one of the earliest applications of an imaging adjunct intraoperatively to examine the brain (possible after the overlying bone was removed). Although older machines and probes were not very user friendly, and resultant images were of poor quality, this is no longer the case. With advances in technology, the modern generation of ultrasound machines and variable frequency tunable probes provide superior image resolution, resulting in a growing interest and application of IUS. Ultrasound is able to characterize lesions and even differentiate various types of tumors.[56],[57],[58],[59],[60],[61] Relative cost-effectiveness, widespread availability, and ease of application combined with the advantage of providing repeated, convenient, on-demand, intraoperative scans in relatively little time, make it an extremely attractive tool. The ability of IUS to provide rapid image updates is a key element in its utility as a resection control tool.[34] However, IUS remains highly operator dependent. The device image orientation and interpretation requires experience, and has a learning curve. Multimodal image fusion (combining preoperative MRI-based navigation with IUS) has shown to be overcoming some of these limitations, leading to improved outcomes.[32],[47],[62],[63],[64],[65] Both two-dimensional (2D) and 3D ultrasound can be combined with navigation. With 3D US, navigating on multiplanar US slices (akin to MRI) is possible and serial resection control becomes easier [Figure 2]. Image artifacts can significantly affect image quality and thereby reduce its utility, especially as the resection proceeds. Ultrasound scans obtained toward the end of resection can have many more artifacts.[66] Artifact minimization is an important skillset for a successful implementation of IUS.[67] Acoustic coupling fluid under development can potentially minimize some of the enhancement artifacts.[66] Regardless of whether one uses 2D or 3D IUS (with or without navigation), the key element remains the correct and optimal use of the basic B-mode gray scale ultrasound image (both its acquisition and image interpretation). Besides the anatomical images, IUS can also provide functional information in the form of color Doppler, power Doppler angiogram (flow independent evaluation of larger vessels), and contrast-enhanced angiosonography (providing accurate microvasculature imaging and perfusion).[68] Elastosonography, which can differentiate tissues based on their stiffness, provides a complementary approach to tissue characterization (as opposed to conventional ultrasound which uses reflected echoes).[69],[70]
Figure 2: Left frontal glioblastoma resection using navigated three-dimensional ultrasound. (a) The operative setup with the navigation (Brainlab Kick®) and BK 5000 ultrasound system. (b) The navigated ultrasound probe with localizer (inset – curvilinear ultrasound probe used). (c) Multimodal image fusion of preoperative magnetic resonance and intraoperative ultrasound images. (d) The multiplanar serially acquired three-dimensional ultrasound images used for resection control

Click here to view


A meta-analysis of IUS studies showed that, when assessed using histological sampling, pooled sensitivity and specificity of IUS in diffuse gliomas was 72 and 93%, respectively, indicating that IUS may miss small tumor residues (low sensitivity) but is more reliable in confirming the absence of residue (high specificity).[18] Another meta-analysis showed that, regardless of the type of IUS modality used, GTR rates up to 77% may be achievable in tumors amenable to complete resection [Table 1].[16] Although few studies have compared IUS directly with IMRI, IMRI is likely to have higher sensitivity.[71],[72] Given the logistics with frequent IMR acquisitions, the use of IUS for frequent intermediate intraoperative updates with a final IMRI control scan may be complementary.[73] The versatility and multifaceted nature of IUS makes it a very useful tool.

Optical imaging

As opposed to IGS, OI techniques enhance visualization of microscopic tumor utilizing an optically active biomarker coupled to a specific detection technique. A variety of OI techniques have been described with varying degrees of utility.[55],[74] Among them, FGS using 5-ALA and SF constitute two of the widely used techniques. Although both utilize the principles of fluorescence imaging, the mechanism of action differs for both the dyes. SF is a passive fluorophore which localizes to the extracellular space in areas of high permeability and breach of blood–brain barrier, following intravenous administration. The uptake occurs within minutes and hence is faster acting than 5-ALA. However, the positive predictive value (PPV) remains an issue with uptake also seen in areas of gliosis, edema, and tissue damage due to surgical manipulation, leading to numerous false positives. Low-dose fluorescein (5–10 mg/kg boluses) with visualization using a special filter (yellow 560 nm) has replaced the older high-dose fluorescein technique with visualization under ambient light and promises better accuracy with fewer false positives [Figure 3].[75] Timing of injection seems to play a significant role in the eventual accuracy of the technique. 5-ALA is a prodrug which is administered orally and converted intracellularly to the active metabolite protoporphyrin IX through the heme pathway.[74] Protoporphyrin IX in the tumor tissue then absorbs the light energy (visible blue 400 nm) and emits it at a higher wavelength (dual emission peak in the visible red range at 635 and 705 nm) highlighting fluorescing cells within the tumor using a suitably modified filter [Figure 4].[76] Being an “active” metabolically transformed agent, it confers higher specificity as compared to sodium-fluorescein. [Table 5] shows the comparative analysis of the two common fluorescence techniques. 5-ALA remains the most widely studied dye, with plenty of literature confirming its advantage in improving the diagnostic accuracy of intraoperative tumor detection as well as therapeutic efficacy for HGG. Although the specificity and PPV are markedly high with 5-ALA, there are some shortcomings which one must be aware of. The peak action only occurs after 4-6 h of oral administration (dose 20 mg/kg) though activity may persist for more than 12 h also, and there exists a theoretical risk of photosensitivity if exposed to sunlight in the immediate postoperative period.
Figure 3: (a and b) Pre- and post-operative images confirmed a gross total resection (image courtesy Dr Francesco Acerbi, Milan, Italy) Sodium-fluorescein guided resection of a malignant glioma. (c and d) Dotted line in corresponds to a necrotic area inside the tumor, which is usually less fluorescent than the more vital counterpart. *Is the fluorescent vital tumor area. Arrow corresponds to nontumoral white matter

Click here to view
Figure 4: Right temporal glioblastoma operated using 5-aminolevulinic acid. (a) Preoperative T1 contrast (left) and T2 magnetic resonance imaging images. (b) Postoperative postcontrast T1 images showing complete excision. (c) Intraoperative image under white light microscope. (d) Same tumor seen under BLUE light revealing strong red fluorescence

Click here to view
Table 5: Comparison between 5-aminolevulinic acid and sodium fluorescein induced fluorescence techniques[76]

Click here to view


5-ALA remains the only fluorescent dye to have been evaluated in a RCT,[35] demonstrating an almost doubling of GTR rates [Table 3]. Since then, there have been numerous studies documenting the diagnostic accuracy as well as therapeutic benefits of ALA and numerous meta-analysis and systematic reviews have consolidated these results [Table 1], [Table 2], [Table 3]. Most report high PPV of strong fluorescence in detecting tumor residue, thereby increasing GTR rates and indirectly improving the survival. False positives still occur, especially in recurrent/previously treated cases.[12] One must be cautious in interpreting these studies as sampling of tissues for ascertaining diagnostic accuracy can lead to biases in the results.[77]

SF has been less studied, but the number of reports is slowly increasing. Although there is no level I evidence, the FLUGLIO study reported comparably high diagnostic accuracy and GTR rates.[30] Further, studies comparing ALA and SF in HGG found no significant differences in the two techniques.[9],[78] A hybrid OI strategy using both has been described and may be potentially useful.[79] Although both 5-ALA and fluorescein have been applied in many other brain tumors (including meningiomas, metastases, pituitary tumors, and even spinal tumors),[22] the bulk of the published evidence is limited to gliomas and benefit in any of the other tumors remains to be conclusively proven.


  Head-to Head Comparison of the Various Modalities Top


It is exceedingly difficult to interpret studies comparing the various modalities because of heterogeneity in the type of tumors selected and the outcomes measured. [Table 1], [Table 2], [Table 3] enumerate some of these studies. A comparative meta-analysis of the various modalities was performed by Eljamel and Mahboob.[19] It was found that GTR after 5-ALA, SF, IUS, and IMRI was 69.1%, 84.4%, 73.4%, and 70%, respectively. The cost/quality-adjusted life in years was lowest for SF and IUS and the highest for IMRI.


  Combined Multimodality Adjuncts Top


As each adjunct has a unique (and mutually exclusive) mechanism of tumor visualization, it is compelling and intuitive to believe that their use in combination is likely to yield synergistic results and augment outcomes. Whereas IGS techniques based on physical characteristics of tissues generally provide tomographic (2D as well as 3D cross-sectional and multiplanar) images interpreted by the naked eye, OI tools provide microscopic/cellular details using aided visualization tools (microscope/spectroscope/detector systems) and are generally restricted to superficial imaging [Figure 5] and [Figure 6]. A combination of modalities is also likely to overcome the limitations of individual techniques and thereby complement each other. 5-ALA when combined with NN leads to a higher specificity as compared to 5-ALA alone,[27] while 5-ALA when used together with IMRI leads to a higher sensitivity.[28] Further, 5-ALA in combination with IMRI has shown to increase the PFS, OS, and GTR rates than with either modality alone.[42],[43],[44],[45] Similarly, IUS in combination with ALA has shown better outcomes with IUS better visualizing the nonenhancing infiltrating component of the tumor which fluorescence may not.[80]
Figure 5: Hyper smart cyber operating theater at the Tokyo Women's Medical University - An operating room where almost all equipment is connected through a network. Time-synchronized data are linked to the navigation location and displayed at the Strategy Desk. Equipped with intraoperative magnetic resonance imaging equipment (0.4Tesla, Hitachi, Tokyo), navigation, and a 4K exoscope (image courtesy – Professor Y Muragaki, Tokyo, Japan)

Click here to view
Figure 6: Comparison of image-guided surgery and optical imaging techniques highlighting their complementary roles

Click here to view


Integrated solutions

With an explosion of information available to the surgeon intraoperatively, technology to integrate the same in real time is essential. State-of-the-art multimodal operating theaters provide a glimpse into future of neurosurgery. The advanced multimodality image-guided operating suite provides real-time anatomic imaging modalities such as radiographs and ultrasonography combined with cross-sectional digital imaging systems such as CT, MRI, and positron emission tomography (PET).[81] In addition, molecular image-guided therapy with the use of multiple molecular probes, such as PET, OI, and targeted mass spectrometry, is available to increase the sensitivity and specificity of cancer detection. The application of these technologies is expected to improve the ability to define tumor margins enabling a more complete excision or to thermally ablate residual tumor. In addition, several navigational devices, robotic devices, and delivery instruments can deploy precise and targeted therapies. The Smart Cyber Operating Theater [Figure 5], a next-generation treatment room developed in Japan, allows online uniform management of devices within the treatment room and enables time synchronization and relocation of their data using a proprietary communication interface.[82] It permits collection of various data such as images obtained from intraoperative modalities and surgical instrument position from surgical navigation systems, as well as surgical field images and biometric patient data and presentation of the same to the surgeon in an actionable format. Incorporation of robotic technology and artificial intelligence algorithms are likely to further augment these solutions.


  Perspectives on the Role of Intraoperative Imaging Adjuncts Top


With a plethora of intraoperative adjuncts available to neurosurgeons today, it is imperative to sift through the vast amounts of published literature and objectively assess their practical utility. Whereas there is little doubt regarding the need for such adjuncts to improve resections, the quality of evidence to support individual techniques is heterogeneous. The present review, though selective in the evaluation of published works, underlines this variability. Differences in study designs, characteristics of patients included, application of adjuncts, and outcome assessments can all contribute to this. It is not a surprise that there is precious little Class I evidence. Inherent problems with the design and conduct of studies assessing diagnostic accuracy of intraoperative adjuncts is well known.[77] The individual surgeon's training and expertise with a particular adjunct may also play a significant role in influencing the outcomes of these techniques and therefore general extrapolation of study results may be erroneous. The issue of defining the “resectability” in diffuse gliomas is also challenging.Further, it is not easy to control for the impact of neuromonitoring adjuncts in determining the final outcomes, especially for tumors close to eloquent regions. Well-designed randomized trials and prospective studies are the need of the hour. Above all, there can be no substitute for judicious surgical decision-making and meticulous adherence to standard microsurgical principles. The adjuncts can only augment and not supplant the surgeon's capabilities.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C, et al. Extent of resection in patients with glioblastoma: Limiting factors, perception of resectability, and effect on survival. J Neurosurg 2012;117:851-9.  Back to cited text no. 1
    
2.
Colditz MJ, Jeffree RL. Aminolevulinic acid (ALA)-protoporphyrin IX fluorescence guided tumour resection. Part 1: Clinical, radiological and pathological studies. J Clin Neurosci 2012;19:1471-4.  Back to cited text no. 2
    
3.
Zhao S, Wu J, Wang C, Liu H, Dong X, Shi C, et al. Intraoperative fluorescence-guided resection of high-grade malignant gliomas using 5-aminolevulinic acid-induced porphyrins: A systematic review and meta-analysis of prospective studies. PLoS One 2013;8:e63682.  Back to cited text no. 3
    
4.
Su X, Huang QF, Chen HL, Chen J. Fluorescence-guided resection of high-grade gliomas: A systematic review and meta-analysis. Photodiagnosis Photodyn Ther 2014;11:451-8.  Back to cited text no. 4
    
5.
Barone DG, Lawrie TA, Hart MG. Image guided surgery for the resection of brain tumors. Cochrane Database Syst Rev 2014;2014:CD009685.  Back to cited text no. 5
    
6.
Eljamel S. 5-ALA fluorescence image guided resection of glioblastoma multiforme: A meta-analysis of the literature. Int J Mol Sci 2015;16:10443-56.  Back to cited text no. 6
    
7.
Ferraro N, Barbarite E, Albert TR, Berchmans E, Shah AH, Bregy A, et al. The role of 5-aminolevulinic acid in brain tumor surgery: A systematic review. Neurosurg Rev 2016;39:545-55.  Back to cited text no. 7
    
8.
Mansouri A, Mansouri S, Hachem LD, Klironomos G, Vogelbaum MA, Bernstein M, et al. The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review. Cancer 2016;122:2469-78.  Back to cited text no. 8
    
9.
Senders JT, Muskens IS, Schnoor R, Karhade AV, Cote DJ, Smith TR, et al. Agents for fluorescence-guided glioma surgery: A systematic review of preclinical and clinical results. Acta Neurochir (Wien) 2017;159:151-67.  Back to cited text no. 9
    
10.
Haider SA, Lim S, Kalkanis SN, Lee IY. The impact of 5-aminolevulinic acid on extent of resection in newly diagnosed high grade gliomas: A systematic review and single institutional experience. J Neurooncol 2019;141:507-15.  Back to cited text no. 10
    
11.
Gandhi S, Tayebi Meybodi A, Belykh E, Cavallo C, Zhao X, Syed MP, et al. Survival outcomes among patients with high-grade glioma treated with 5-aminolevulinic acid-guided surgery: A systematic review and meta-analysis. Front Oncol 2019;9:620.  Back to cited text no. 11
    
12.
Broekx S, Weyns F, De Vleeschouwer S. 5-Aminolevulinic acid for recurrent malignant gliomas: A systematic review. Clin Neurol Neurosurg 2020;195:105913.  Back to cited text no. 12
    
13.
Kubben PL, ter Meulen KJ, Schijns OE, ter Laak-Poort MP, van Overbeeke JJ, van Santbrink H. Intraoperative MRI-guided resection of glioblastoma multiforme: A systematic review. Lancet Oncol 2011;12:1062-70.  Back to cited text no. 13
    
14.
Lo YT, Lee H, Shui C, Lamba N, Korde R, Devi S, et al. Intraoperative magnetic resonance imaging for low-grade and high-grade gliomas: What is the evidence? A meta-analysis. World Neurosurg 2021;149:232-43.e3.  Back to cited text no. 14
    
15.
Golub D, Hyde J, Dogra S, Nicholson J, Kirkwood KA, Gohel P, et al. Intraoperative MRI versus 5-ALA in high-grade glioma resection: A network meta-analysis. J Neurosurg 2020;1-15. doi: 10.3171/2019.12.JNS191203. Online ahead of print.  Back to cited text no. 15
    
16.
Mahboob S, McPhillips R, Qiu Z, Jiang Y, Meggs C, Schiavone G, et al. Intraoperative ultrasound-guided resection of gliomas: A meta-analysis and review of the literature. World Neurosurg 2016;92:255-63.  Back to cited text no. 16
    
17.
Zhang G, Li Z, Si D, Shen L. Diagnostic ability of intraoperative ultrasound for identifying tumor residual in glioma surgery operation. Oncotarget 2017;8:73105-14.  Back to cited text no. 17
    
18.
Trevisi G, Barbone P, Treglia G, Mattoli MV, Mangiola A. Reliability of intraoperative ultrasound in detecting tumor residual after brain diffuse glioma surgery: A systematic review and meta-analysis. Neurosurg Rev 2020;43:1221-33.  Back to cited text no. 18
    
19.
Eljamel MS, Mahboob SO. The effectiveness and cost-effectiveness of intraoperative imaging in high-grade glioma resection; a comparative review of intraoperative ALA, fluorescein, ultrasound and MRI. Photodiagnosis Photodyn Ther 2016;16:35-43.  Back to cited text no. 19
    
20.
Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: A prospective study in 52 consecutive patients. J Neurosurg 2000;93:1003-13.  Back to cited text no. 20
    
21.
Nabavi A, Thurm H, Zountsas B, Pietsch T, Lanfermann H, Pichlmeier U, et al. Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: A phase ii study. Neurosurgery 2009;65:1070-6.  Back to cited text no. 21
    
22.
Marbacher S, Klinger E, Schwyzer L, Fischer I, Nevzati E, Diepers M, et al. Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases. Neurosurg Focus 2014;36:E10.  Back to cited text no. 22
    
23.
Valdés PA, Jacobs V, Harris BT, Wilson BC, Leblond F, Paulsen KD, et al. Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery. J Neurosurg 2015;123:771-80.  Back to cited text no. 23
    
24.
Yamada S, Muragaki Y, Maruyama T, Komori T, Okada Y. Role of neurochemical navigation with 5-aminolevulinic acid during intraoperative MRI-guided resection of intracranial malignant gliomas. Clin Neurol Neurosurg 2015;130:134-9.  Back to cited text no. 24
    
25.
Moiyadi AV, Sridhar E, Shetty P, Madhugiri VS, Solanki S. What you see and what you don't-Utility and pitfalls during fluorescence guided resections of gliomas using 5-aminolevulinic acid. Neurol India 2018;66:1087-93.  Back to cited text no. 25
[PUBMED]  [Full text]  
26.
Lau D, Hervey-Jumper SL, Chang S, Molinaro AM, McDermott MW, Phillips JJ, et al. A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas. J Neurosurg 2016;124:1300-9.  Back to cited text no. 26
    
27.
Panciani PP, Fontanella M, Garbossa D, Agnoletti A, Ducati A, Lanotte M. 5-Aminolevulinic acid and neuronavigation in high-grade glioma surgery: Results of a combined approach. Neurocirugia (Astur) 2012;23:23-8.  Back to cited text no. 27
    
28.
Coburger J, Engelke J, Scheuerle A, Thal DR, Hlavac M, Wirtz CR, et al. Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA-enhanced intraoperative MRI at the border of contrast-enhancing lesions: A prospective study based on histopathological assessment. Neurosurg Focus 2014;36:E3.  Back to cited text no. 28
    
29.
Hauser SB, Kockro RA, Actor B, Sarnthein J, Bernays RL. Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery: A Histology-Based Evaluation. Neurosurgery 2016;78:475-83.  Back to cited text no. 29
    
30.
Acerbi F, Broggi M, Schebesch KM, Höhne J, Cavallo C, De Laurentis C, et al. Fluorescein-guided surgery for resection of high-grade gliomas: A multicentric prospective phase II study (FLUOGLIO). Clin Cancer Res 2018;24:52-61.  Back to cited text no. 30
    
31.
Rohde V, Coenen VA. Intraoperative 3-dimensional ultrasound for resection control during brain tumour removal: Preliminary results of a prospective randomized study. Acta Neurochir Suppl 2011;109:187-90.  Back to cited text no. 31
    
32.
Coburger J, Scheuerle A, Kapapa T, Engelke J, Thal DR, Wirtz CR, et al. Sensitivity and specificity of linear array intraoperative ultrasound in glioblastoma surgery: A comparative study with high field intraoperative MRI and conventional sector array ultrasound. Neurosurg Rev 2015;38:499-509.  Back to cited text no. 32
    
33.
Munkvold BKR, Jakola AS, Reinertsen I, Sagberg LM, Unsgård G, Solheim O. The diagnostic properties of intraoperative ultrasound in glioma surgery and factors associated with gross total tumor resection. World Neurosurg 2018;115:e129-36.  Back to cited text no. 33
    
34.
Shetty P, Yeole U, Singh V, Moiyadi A. Navigated ultrasound-based image guidance during resection of gliomas: Practical utility in intraoperative decision-making and outcomes. Neurosurg Focus 2021;50:E14.  Back to cited text no. 34
    
35.
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol 2006;7:392-401.  Back to cited text no. 35
    
36.
Stummer W, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, et al. Counterbalancing risks and gains from extended resections in malignant glioma surgery: A supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article. J Neurosurg 2011;114:613-23.  Back to cited text no. 36
    
37.
Schucht P, Beck J, Abu-Isa J, Andereggen L, Murek M, Seidel K, et al. Gross total resection rates in contemporary glioblastoma surgery: Results of an institutional protocol combining 5-aminolevulinic acid intraoperative fluorescence imaging and brain mapping. Neurosurgery 2012;71:927-35.  Back to cited text no. 37
    
38.
Díez Valle R, Slof J, Galván J, Arza C, Romariz C, Vidal C, et al. Observational, retrospective study of the effectiveness of 5-aminolevulinic acid in malignant glioma surgery in Spain (The VISIONA study). Neurologia 2014;29:131-8.  Back to cited text no. 38
    
39.
Hickmann AK, Nadji-Ohl M, Hopf NJ. Feasibility of fluorescence-guided resection of recurrent gliomas using five-aminolevulinic acid: Retrospective analysis of surgical and neurological outcome in 58 patients. J Neurooncol 2015;122:151-60.  Back to cited text no. 39
    
40.
Teixidor P, Arráez MÁ, Villalba G, Garcia R, Tardáguila M, González JJ, et al. Safety and efficacy of 5-aminolevulinic acid for high grade glioma in usual clinical practice: A prospective cohort study. PLoS One 2016;11:e0149244.  Back to cited text no. 40
    
41.
Picart T, Armoiry X, Berthiller J, Dumot C, Pelissou-Guyotat I, Signorelli F, et al. Is fluorescence-guided surgery with 5-ala in eloquent areas for malignant gliomas a reasonable and useful technique? Neurochirurgie 2017;63:189-96.  Back to cited text no. 41
    
42.
Eyüpoglu IY, Hore N, Savaskan NE, Grummich P, Roessler K, Buchfelder M, et al. Improving the extent of malignant glioma resection by dual intraoperative visualization approach. PLoS One 2012;7:e44885.  Back to cited text no. 42
    
43.
Roder C, Bisdas S, Ebner FH, Honegger J, Naegele T, Ernemann U, et al. Maximizing the extent of resection and survival benefit of patients in glioblastoma surgery: High-field iMRI versus conventional and 5-ALA-assisted surgery. Eur J Surg Oncol 2014;40:297-304.  Back to cited text no. 43
    
44.
Schatlo B, Fandino J, Smoll NR, Wetzel O, Remonda L, Marbacher S, et al. Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery. Neuro Oncol 2015;17:1560-7.  Back to cited text no. 44
    
45.
Coburger J, Hagel V, Wirtz CR, König R. Surgery for glioblastoma: Impact of the combined use of 5-aminolevulinic acid and intraoperative MRI on extent of resection and survival. PLoS One 2015;10:e0131872.  Back to cited text no. 45
    
46.
Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V. Intraoperative MRI guidance and extent of resection in glioma surgery: A randomised, controlled trial. Lancet Oncol 2011;12:997-1003.  Back to cited text no. 46
    
47.
Moiyadi AV, Kannan S, Shetty P. Navigated intraoperative ultrasound for resection of gliomas: Predictive value, influence on resection and survival. Neurol India 2015;63:727-35.  Back to cited text no. 47
[PUBMED]  [Full text]  
48.
Smith H, Taplin A, Syed S, Adamo MA. Correlation between intraoperative ultrasound and postoperative MRI in pediatric tumor surgery. J Neurosurg Pediatr 2016;18:578-84.  Back to cited text no. 48
    
49.
Wirtz CR, Albert FK, Schwaderer M, Heuer C, Staubert A, Tronnier VM, et al. The benefit of neuronavigation for neurosurgery analyzed by its impact on glioblastoma surgery. Neurol Res 2000;22:354-60.  Back to cited text no. 49
    
50.
Kurimoto M, Hayashi N, Kamiyama H, Nagai S, Shibata T, Asahi T, et al. Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: A single-institution retrospective study. Minim Invasive Neurosurg 2004;47:278-83.  Back to cited text no. 50
    
51.
Willems PW, Taphoorn MJ, Burger H, Berkelbach van der Sprenkel JW, Tulleken CA. Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: A randomized controlled trial. J Neurosurg 2006;104:360-8.  Back to cited text no. 51
    
52.
Wu JS, Zhou LF, Tang WJ, Mao Y, Hu J, Song YY, et al. Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: A prospective, controlled study in patients with gliomas involving pyramidal tracts. Neurosurgery 2007;61:935-48.  Back to cited text no. 52
    
53.
Rutka JT. Editorial. Classes of evidence in neurosurgery. J Neurosurg 2017;126:1747-8.  Back to cited text no. 53
    
54.
Hadley MN, Walters BC, Grabb PA, Oyesiku NM, Przybylski GJ, Resnick DK, et al. Methodology of guideline development. Neurosurgery 2002;50 (3 Suppl):S2-6. doi: 10.1097/00006123-200203001-00004.  Back to cited text no. 54
    
55.
Moiyadi AV, Shaikh ST, Singh VJ. Optical imaging in neuro-oncological surgery – Review of techniques and comparative analysis. Curr Pract Neurosci 2020;2 (3);1-12.  Back to cited text no. 55
    
56.
Auer LM, van Velthoven V. Intraoperative ultrasound (US) imaging. Comparison of pathomorphological findings in US and CT. Acta Neurochir (Wien) 1990;104:84-95.  Back to cited text no. 56
    
57.
Chen SY, Chiou T, Chiu W, Su C-F, Lin S-Z, Wang S-G, et al. Application of intraoperative ultrasound for brain surgery. Tzu Chi Med J 2004;16:85-92.  Back to cited text no. 57
    
58.
Cengiz C, Keramettin A. Intraoperative ultrasonographic characteristics of malignant intracranial lesions. Neurol India 2005;53:208-11.  Back to cited text no. 58
[PUBMED]  [Full text]  
59.
Wang J, Liu X, Hou WH, Dong G, Wei Z, Zhou H, et al. The relationship between intra-operative ultrasonography and pathological grade in cerebral glioma. J Int Med Res 2008;36:1426-34.  Back to cited text no. 59
    
60.
Mair R, Heald J, Poeata I, Ivanov M. A practical grading system of ultrasonographic visibility for intracerebral lesions. Acta Neurochir (Wien) 2013;155:2293-8.  Back to cited text no. 60
    
61.
Baskan O, Silav G, Sari R, Canoz O, Elmaci I. Relationship of intraoperative ultrasound characteristics with pathological grades and Ki-67 proliferation index in intracranial gliomas. J Med Ultrason (2001) 2015;42:231-7.  Back to cited text no. 61
    
62.
Munkvold BK, Bø HK, Jakola AS, Reinertsen I, Berntsen EM, Unsgård G, et al. Tumor volume assessment in low-grade gliomas: A comparison of preoperative magnetic resonance imaging to coregistered intraoperative 3-dimensional ultrasound recordings. Neurosurgery 2018;83:288-96.  Back to cited text no. 62
    
63.
Siekmann M, Lothes T, König R, Wirtz CR, Coburger J. Experimental study of sector and linear array ultrasound accuracy and the influence of navigated 3D-reconstruction as compared to MRI in a brain tumor model. Int J Comput Assist Radiol Surg 2018;13:471-8.  Back to cited text no. 63
    
64.
Moiraghi A, Pallud J. Intraoperative ultrasound techniques for cerebral gliomas resection: Usefulness and pitfalls. Ann Transl Med 2020;8:523.  Back to cited text no. 64
    
65.
Renovanz M, Hickmann AK, Henkel C, Nadji-Ohl M, Hopf NJ. Navigated versus non-navigated intraoperative ultrasound: Is there any impact on the extent of resection of high-grade gliomas? A retrospective clinical analysis. J Neurol Surg A Cent Eur Neurosurg 2014;75:224-30.  Back to cited text no. 65
    
66.
Unsgård G, Sagberg LM, Müller S, Selbekk T. A new acoustic coupling fluid with ability to reduce ultrasound imaging artefacts in brain tumor surgery – A phase I study. Acta Neurochir (Wien) 2019;161:1475-86.  Back to cited text no. 66
    
67.
Selbekk T, Jakola AS, Solheim O, Johansen TF, Lindseth F, Reinertsen I, et al. Ultrasound imaging in neurosurgery: Approaches to minimize surgically induced image artefacts for improved resection control. Acta Neurochir (Wien) 2013;155:973-80.  Back to cited text no. 67
    
68.
Kearns KN, Sokolowski JD, Chadwell K, Chandler M, Kiernan T, Prada F, et al. The role of contrast-enhanced ultrasound in neurosurgical disease. Neurosurg Focus 2019;47:E8.  Back to cited text no. 68
    
69.
Prada F, Del Bene M, Rampini A, Mattei L, Casali C, Vetrano IG, et al. Intraoperative Strain Elastosonography in Brain Tumor Surgery. Oper Neurosurg (Hagerstown) 2019;17:227-36.  Back to cited text no. 69
    
70.
Cepeda S, Barrena C, Arrese I, Fernandez-Pérez G, Sarabia R. Intraoperative ultrasonographic elastography: A semi-quantitative analysis of brain tumor elasticity patterns and peritumoral region. World Neurosurg 2020;135:e258-70.  Back to cited text no. 70
    
71.
Gerganov VM, Samii A, Akbarian A, Stieglitz L, Samii M, Fahlbusch R. Reliability of intraoperative high-resolution 2D ultrasound as an alternative to high-field strength MR imaging for tumor resection control: A prospective comparative study. J Neurosurg 2009;111:512-9.  Back to cited text no. 71
    
72.
Gerganov VM, Samii A, Giordano M, Samii M, Fahlbusch R. Two-dimensional high-end ultrasound imaging compared to intraoperative MRI during resection of low-grade gliomas. J Clin Neurosci 2011;18:669-73.  Back to cited text no. 72
    
73.
Tronnier VM, Bonsanto MM, Staubert A, Knauth M, Kunze S, Wirtz CR. Comparison of intraoperative MR imaging and 3D-navigated ultrasonography in the detection and resection control of lesions. Neurosurg Focus 2001;10:E3.  Back to cited text no. 73
    
74.
Belykh E, Shaffer KV, Lin C, Byvaltsev VA, Preul MC, Chen L. Blood-brain barrier, blood-brain tumor barrier, and fluorescence-guided neurosurgical oncology: Delivering optical labels to brain tumors. Front Oncol 2020;10:739.  Back to cited text no. 74
    
75.
Acerbi F, Broggi M, Eoli M, Anghileri E, Cavallo C, Boffano C, et al. Is fluorescein-guided technique able to help in resection of high-grade gliomas? Neurosurg Focus 2014;36:E5.  Back to cited text no. 75
    
76.
Moiyadi AV, Stummer W. δ-Aminolevulinic acid-induced fluorescence-guided resection of brain tumors. Neurol India 2015;63:155-65.  Back to cited text no. 76
[PUBMED]  [Full text]  
77.
Stummer W, Koch R, Valle RD, Roberts DW, Sanai N, Kalkanis S, et al. Intraoperative fluorescence diagnosis in the brain: A systematic review and suggestions for future standards on reporting diagnostic accuracy and clinical utility. Acta Neurochir (Wien) 2019;161:2083-98.  Back to cited text no. 77
    
78.
Hansen RW, Pedersen CB, Halle B, Korshoej AR, Schulz MK, Kristensen BW, et al. Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: A single-center retrospective study. J Neurosurg 2019;Oct 4:1-8. doi: 10.3171/2019.6.JNS191531. Online ahead of print. Suero Molina E, Wölfer J, Ewelt C, Ehrhardt A, Brokinkel B, Stummer W. Dual-labeling with 5-aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas: Technical note. J Neurosurg 2018;128:399-405.  Back to cited text no. 78
    
79.
Moiyadi A, Shetty P. Navigable intraoperative ultrasound and fluorescence-guided resections are complementary in resection control of malignant gliomas: One size does not fit all. J Neurol Surg A Cent Eur Neurosurg 2014;75:434-41.  Back to cited text no. 79
    
80.
Jolesz FA. Intraoperative imaging in neurosurgery: Where will the future take us? Acta Neurochir Suppl 2011;109:21-5.  Back to cited text no. 80
    
81.
Okamoto J, Masamune K, Iseki H, Muragaki Y. Development concepts of a Smart Cyber Operating Theater (SCOT) using ORiN technology. Biomed Tech (Berl) 2018;63:31-7.  Back to cited text no. 81
    
82.
Moiyadi AV. Glioma surgery: The art and science. Int J Neurooncol 2018;1:6-10.  Back to cited text no. 82
  [Full text]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Methodology
Head-to Head Com...
Combined Multimo...
Perspectives on ...
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed130    
    Printed2    
    Emailed0    
    PDF Downloaded15    
    Comments [Add]    

Recommend this journal