36
1 Title page Navigated Intraoperative Ultrasonography for Brain tumors technique, utility and benefits in neuro- oncology A pictorial essay Ujwal Yeole, M.Ch, Vikas Singh, M.Ch, Ajit Mishra, M.Ch, Salman Shaikh, M.Ch, Prakash Shetty, M.Ch, Aliasgar Moiyadi, M.Ch. Neurosurgery Services, Dept of Surgical oncology, Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, India. 400012. 1. Ujwal Yeole, M.Ch, Fellow in Clinical Neurosurgical-Oncology. Email: [email protected] 2. Vikas Singh, M.Ch, Assistant Professor, Department of Neurosurgery. Email: [email protected] 3. Ajit Mishra, M.Ch, Fellow in Clinical Neurosurgical-Oncology. Email: [email protected] 4. Salman Shaikh, M.Ch, Fellow in Clinical Neurosurgical-Oncology. Email: [email protected] 5. Prakash Shetty, M.Ch, Professor, Department of Neurosurgery. Email: [email protected] 6. Aliasgar Moiyadi, Professor & Chief Neurosurgeon. Email: [email protected] ORCID: 0000-0002-4082-2004 Accepted Article

Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

  • Upload
    others

  • View
    0

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

1

Title page

Navigated Intraoperative Ultrasonography for Brain tumors – technique, utility and benefits in neuro-

oncology –A pictorial essay

Ujwal Yeole, M.Ch, Vikas Singh, M.Ch, Ajit Mishra, M.Ch, Salman Shaikh, M.Ch, Prakash Shetty, M.Ch, Aliasgar

Moiyadi, M.Ch.

Neurosurgery Services, Dept of Surgical oncology, Tata Memorial Centre and Homi Bhabha National Institute,

Mumbai, India. 400012.

1. Ujwal Yeole, M.Ch, Fellow in Clinical Neurosurgical-Oncology.

Email: [email protected]

2. Vikas Singh, M.Ch, Assistant Professor, Department of Neurosurgery.

Email: [email protected]

3. Ajit Mishra, M.Ch, Fellow in Clinical Neurosurgical-Oncology.

Email: [email protected]

4. Salman Shaikh, M.Ch, Fellow in Clinical Neurosurgical-Oncology.

Email: [email protected]

5. Prakash Shetty, M.Ch, Professor, Department of Neurosurgery.

Email: [email protected]

6. Aliasgar Moiyadi, Professor & Chief Neurosurgeon.

Email: [email protected]

ORCID: 0000-0002-4082-2004

Acce

pted

Arti

cle

Page 2: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

2

Corresponding author:

Aliasgar Moiyadi,

Professor & Chief Neurosurgeon,

Neurosurgery Services, Dept of Surgical oncology, Tata Memorial Centre and Homi Bhabha National Institute,

Mumbai, India. 400012.

Email: [email protected]

Contact: +91 9324696948

ORCID: 0000-0002-4082-2004

Running title: Navigated Intraoperative Ultrasound.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-

for-profit sectors.

Conflict of Interests: The authors declare that they have no conflict of interest.

Acknowledgements: None

Author’s contributions: All authors contributed to the study conception and design. AM conceptualized the paper.

AM, PS and VS were the operating surgeons for the cases on which the paper is based. Material preparation, data

collection and analysis were performed by UY and AM. The first draft of the manuscript was written by UY and

AM and all authors commented on previous versions of the manuscript. All authors read and approved the final

manuscript.

Acce

pted

Arti

cle

Page 3: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

1

Navigated Intraoperative Ultrasonography for Brain tumors – technique, utility and 1

benefits in neuro-oncology – A pictorial essay 2

3

Abstract: 4

Intraoperative imaging has become one of the most important adjuncts in Neurosurgery 5

especially in surgery of intra-axial tumors. Navigation and intraoperative MR have their 6

limitations. Intraoperative ultrasound has emerged as a versatile and multifaceted tool for this 7

purpose. With advances in technology of the ultrasound scanners and newer multifunctional 8

probes the potential of IOUS is increasingly being utilized in resection of tumors. Addition of 9

image guidance to IOUS has exponentially increased the power of IOUS. Navigated US (nUS) 10

can now overcome many of the limitations of conventional standalone 2DUS. In this pictorial 11

essay, we outline our technique of performing nUS (both 2D and 3D) during resection of intra-12

axial tumors with illustrated examples highlighting the various steps and benefits of each. 13

14

15

Key words: Intraoperative Ultrasound, Navigated Ultrasound, brain tumors, intraoperative 16

imaging 17

18

19

Acce

pted

Arti

cle

Page 4: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

2

Introduction: 20

Intraoperative updated imaging has become an important component of most brain tumor 21

surgeries. Conventional image-guided surgery (IGS or neuro-navigation) which relies on 22

preoperatively acquired CT or MR images, is limited by the problem of brain-shift and 23

deformation (once dura is opened and brain is manipulated) rendering such preoperatively 24

acquired “maps” inaccurate and unusable [1]. This has led to the proliferation of intraoperative 25

imaging tools to update and provide “corrected” images. Intraoperative CT (IOCT) is not very 26

useful due to inherent lack of soft tissue resolution and the problem of radiation exposure. 27

Intraoperative MR (IOMR) has been regarded as the gold standard in this context but remains a 28

logistically and financially unattractive option in most neurosurgical settings. Intraoperative 29

ultrasonography (IOUS) has proven to be a useful, easily available and cost-effective tool during 30

neuro-oncological procedures, overcoming the limitations posed by IOMR [2][3]. Standard 2-D 31

grey-scale ultrasound (2DUS) provides rapid, repeated, real-time updates intraoperatively 32

without altering the surgical workflow. Advances in US technology have led to development of 33

newer generation scanners specifically designed for intracranial application. With superior image 34

quality combined with the doppler and angiography as well as the newer US applications like 35

contrast-enhanced US (CEUS) and elastosonography, IOUS has become arguably the imaging 36

modality of choice in neuro-oncological surgeries. With minimal alteration in the surgical 37

workflow (unlike MR) and the ease of repeated use, IOUS is an attractive tool. Having said that, 38

2DUS does pose certain limitations essentially related to the problems of orientating a limited 39

field of view and interpreting planar images in unconventional planes. Navigated ultrasound 40

(nUS) utilizing either 2D (n2DUS) or 3D (n3DUS) volumes helps overcome many of the 41

limitations of standalone 2DUS. 42

Acce

pted

Arti

cle

Page 5: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

3

We outline our technique of performing n3DUS during brain tumour surgeries describing the 43

technical nuances and discuss with illustrative cases the spectrum of applications and benefits. 44

We have used a commercially available high-end ultrasound scanner bk5000 (® BK Medical, 45

Denmark) digitally integrated with Brainlab KICK navigation with Ultrasound navigation 46

software (®BRAINLAB AG, Munich, Germany) to perform n3DUS in 34 cases. The present 47

paper focusses on the application of this system during brain tumour surgeries. The setup, 48

detailed insonation parameters and operating room workflow are provided in supplementary 49

material as well as figures 1-3. 50

2DUS Acquisition: After completing the craniotomy, curved linear probe with a small footprint 51

(29 x 10 mm) and frequency range of 5-13MHz (Craniotomy N13C5 tansducer, ®BK Medical, 52

Denmark) is brought into the surgical field and a wide transdural 2DUS scan of the entire 53

exposed surface is performed (Fig 4). Adjusting the parameters (depth, gain, time-gain control) 54

helps optimize the images. We repeat the US acquisition after opening the dura again (as dural 55

calcifications may sometimes interfere with optimal insonation). This helps characterize the 56

lesion (extent, echogenicity, internal variability, margins, cysts, calcific shadows) and survey the 57

surrounding anatomical landmarks for better orientation. Falx (linear hyperechoic structure), 58

ventricles (anechoic, bilaterally symmetrical) and choroid plexus (densely hyperechoic tufts 59

within the ventricles) are useful starting points. Performing careful orthogonal scans (in two 60

planes preferably in conventional imaging planes axial, coronal, sagittal -ACS) can aid to 61

generate a mental 3D picture of the entire operative field and help in getting oriented –as shown 62

in figure 5. However, it is often difficult to do this with a 2DUS, (challenges of location and size 63

of craniotomy) unless one is an expert operator. At this point, additional imaging with doppler, 64

Acce

pted

Arti

cle

Page 6: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

4

angiography, CEUS or elastosonography can also be performed (though we do not do that 65

routinely) to further characterize the lesion if needed. 66

Navigated 2DUS : n2DUS scan can then be immediately acquired in a pre-calibrated system by 67

just attaching the navigation localizer to the probe (Fig. 3). As the probe is moved in the surgical 68

field, the corresponding 2DUS is visualized in real-time on the navigation screen superimposed 69

on the co-displayed MR scans in the corresponding plane as well as the virtual representation of 70

the probe in the surgical field (Fig. 6). This multimodal image display instantly makes it easier to 71

understand the plane of insonation which may not be a true anatomical plane and helps to 72

manually adjust and realign the US plane in a conventional true ACS plane if needed (Fig. 7). 73

Further, it is easier to identify anatomical landmarks in the US image (especially for a novice 74

who may find it difficult to interpret US image) by correlating with the corresponding MR image 75

which is in the same plane. However, multiplanar US imaging is still not possible with n2DUS 76

unless the probe is rotated in different planes itself. Hence, we prefer performing a 3DUS before 77

commencing resection. (Fig. 8). 78

Navigated 3DUS– After performing a live n2DUS, the probe is swept along the operative field 79

of interest capturing a series of 2DUS images which are reconstructed into a 3D volume (3D 80

sweep). It is important to utilize the entire exposed surface to generate as large a volume as 81

possible. The system permits a single continuous sweep and hence the best sweep which will 82

encompass as much of the representative tumour area as well as surrounding brain is first 83

“practised” on live n2DUS mode, which also ensures that during the actual 3DUS acquisition, 84

there are no line-of-sight problems with the navigation system. The actual sweep is then 85

completed by slowly tilting and translating the probe over the surface of the dura (or brain) from 86

one end of the craniotomy to the other along the chosen direction. Continuous feedback from the 87

Acce

pted

Arti

cle

Page 7: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

5

live n2DUS screen provides complete control over the quality and content of this 3D acquisition. 88

Within 20-30 seconds, the system computes the 3D volume. Once this is done, the probe is set 89

aside and using the navigation probe the US image depicted on the navigation screen in 90

multiplanar ACS views (co-displayed with MR image) can be used for navigation. (Fig. 8) This 91

3D US-MR image fusion technique greatly improves the ease of orientation and interpretation of 92

US images and compensates for the limited field-of-view of the US. The MR image also provide 93

additional functional information (cortical eloquent areas and tracts) which can be segmented 94

and superimposed on the subsequently acquired US image, thus providing the all-important 95

functional information lacking in US image (Fig. 9). One of the problems with using 96

preoperative MR-based navigation is the loss of accuracy once the dura is opened and CSF is 97

released causing a change in the relative position of the brain and intracranial contents – the 98

phenomenon of brainshift. This brainshift can also be identified using n3DUS and may even be 99

quantified (Fig. 10). Though we use the overlay fMRI and tractography information, we rely on 100

confirmatory intraoperative neuromonitoring using monopolar (under anaesthesia) or bipolar 101

(awake) stimulation during surgeries in all tumours close to eloquent regions. Surgical resection 102

then follows standard micro-neurosurgical principles. We prefer using an en bloc resection 103

strategy for all low grade and most high-grade intra-axial lesions. The IOUS blends seamlessly 104

into the surgical workflow without much discomfort to either patient (if awake) and the surgeon. 105

Resection control scans – As the resection progresses frequent US updates are obtained. Prior to 106

each US scan, the resection cavity is thoroughly rinsed of debris with copious saline and 107

hemostasis achieved meticulously. The table position can be adjusted to ensure that the cavity is 108

as vertical as possible and then filled with adequate saline. It is imperative, always to ensure that 109

the images are of good quality and free of artefacts. Insonation is repeated in the same sequence 110

Acce

pted

Arti

cle

Page 8: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

6

as for the pre-resection US scans (live 2DUS sweeps followed by 3DUS acquisition if needed). 111

Occasionally only live 2DUS updates are done to obtain a rapid review of the extent of resection 112

or to check and reorient the progress (Fig. 11). Even with n2DUS, it is important to keep in mind 113

the plane of the previously acquired 2DUS scans to avoid misinterpreting presence or absence of 114

residue, especially when comparing non-coplanar images. (Fig. 12). The challenge is to obtain 115

images in same plane repeatedly when a very small residue needs to be detected. More 116

importantly, once the probe is removed from the operative site, the images are no longer 117

available for review and for finding the exact location of the residue. With n3DUS, once the 118

navigator is brought into the field comparative evaluation of the serial temporally acquired US 119

image can be performed and the exact location of the residue can be pinpointed and further 120

resected with confidence (Fig. 12 and 13). Multiple such 3DUS scans can be repeatedly acquired 121

as the resection progresses. Brainshift across the subsequent US scans can also be appreciated 122

(Fig. 14). Besides the conventional axial, coronal and sagittal views, it is possible to represent 123

the acquired images in a more user-intuitive inline view. The inline views depict the volume in a 124

plane parallel to the plane of surgical view thereby providing more practical orientation. 125

Combining two such mutually orthogonal views is very useful in orientating the operative cavity 126

with respect to the acquired images (Fig. 15). Each 3DUS acquisition takes not more than 1-2 127

minutes overall, adding negligible time to the overall procedure. 128

129

130

Acce

pted

Arti

cle

Page 9: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

7

Discussion: 131

IGS has become the need of the hour, especially in brain tumours where the importance of the 132

extent of resection is well-established. One of the major reasons for incomplete resections is the 133

inadvertent residue which is missed by conventional surgical examination of the operative cavity 134

[4]. Navigation is of limited value by itself. To maximize the resection, various intraoperative 135

tools are available including fluorescence, ultrasound, and MR of which the IOUS is the most 136

cost-effective [5]. Not only this, IOUS is mostly available in all setups and is a versatile tool with 137

many applications during tumour surgery [2][3]. By itself, 2DUS is a useful tool during targeting 138

and resection control of tumours. With advances in US technology, the quality of acquired 139

images and functionality of US systems has greatly increased. There remains the issue of 140

subjectivity and the technique is user dependent. Neurosurgeons by training are ill equipped to 141

perform and interpret US scans. Coupled with the unconventional surgical planes during 142

craniotomy exposures, and incomplete (lack of full head) views of the IOUS, there is 143

considerable disorientation, making the learning curve steeper. Also, the wonderful images 144

provided by the ultrasound needs to be memorized by the surgeon as once the US probe is 145

removed from the surgical field, these image are no longer available and the surgeon must rely 146

on the mental reconstruction to proceed with further resection which can be challenging when 147

chasing smaller tumour remnants in proximity of critical and eloquent structures. However, as 148

we have demonstrated in this paper, using navigation and image fusion, the potential benefits of 149

US can be unlocked. 2DUS, n2DUS and n3DUS have incremental benefits as shown in Fig. 16 150

building on the strengths of each component (US and navigation). 151

Image fusion with MR image allows US image to be co-displayed with the MR image. This 152

improves image interpretation (one can use the MR image to learn and understand the US image) 153

Acce

pted

Arti

cle

Page 10: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

8

as also overall orientation of the surgical field [6]. Tracking the US probe during the acquisition 154

of the US image intraoperatively is the key step to be able to navigate with the US image. 155

Subsequently some systems (as the one described above) can acquire and reconstruct 3D 156

volumetric US scans which then can be reformatted in any chosen plane of representation such 157

as ACS views. They allow instant re-orientation of the US anatomy in the standard views which 158

makes learning easier in the initial stages of training. n3DUS also permits serial display and 159

comparison of multiple resection control US scans performed sequentially, thereby allowing for 160

accurate assessment of small residual remnants (Fig. 8 and 9). Using nUS, Renovanz et al 161

showed that the sensitivity and specificity of detecting tumour remnants is increased as 162

compared to non-nUS [7]. More such comparative studies are needed to critically analyse the 163

benefits of nUS. Whereas most systems require the preoperative MRI to be co-displayed, some 164

navigated US systems can even use just the 3DUS data for navigation providing a direct-165

navigated US option. In our earlier experience with such a system, we found this to be very 166

convenient especially in situations where a preoperative MR sequence suitable for navigation is 167

not available [8]. This however requires a level of proficiency in using and interpreting US 168

image which may be learnt rather quickly when using the co-display image fusion during the 169

early part of the learning curve. nUS can also demonstrate the brain-shift and is also useful for 170

compensating the same. (Fig. 10 and 14) [6]. Though not always accurate, it is best to continue 171

to rely on the most recently updated US image (and subsequent resection-control scans) for 172

assessing the operative field as they represent the true status and should be relied upon for 173

making intraoperative decisions. Basing intraoperative assessments on the updated US image 174

with the MR image setting up a roadmap is the best way to work with nUS. 175

Acce

pted

Arti

cle

Page 11: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

9

At our centre, we have been using IOUS for over 12 years graduated to nUS which we have been 176

using for almost 8 years now. The initial phase of the learning curve is longer, but use of 177

navigated US can substantially shorten this phase. In our experience, IOUS is a very useful tool 178

for all kinds of brain tumours [3,9]. It is particularly useful for targeted biopsies [10] as well as 179

resection of intra-axial tumours [11-14]. Large systematic reviews and meta-analyses have also 180

found IOUS to be a very useful adjunct to improve resections in gliomas [15 -16]. Considering 181

its easy availability and relatively low cost, this is one tool which should be increasingly adopted 182

by neurosurgeons. Acquiring a good US scan remains the cornerstone of this technique and 183

cannot be compensated for by any image fusion. Moreover, post resection artefacts are 184

troublesome and need to be minimized for accurate interpretation. [17]. Despite the challenges, 185

the learning curve can be quickly climbed with dedicated training and the frequent use of 186

navigated ultrasound. Interpretation of the post-resection US scan remains a key factor in its role 187

as a tool for resection control. Diagnostic accuracy of US compared to postoperative MRI [18] as 188

well as pathological tumor confirmation [19] is reported between 60-100%. However, 189

comparison across studies is difficult due to lack of uniform criteria of US residue and the gold 190

standard in all studies. 191

192

Conclusion: Navigated ultrasound is a useful addition to the intraoperative-imaging 193

armamentarium of the neurosurgeon. It combines the benefits of real-ime US imaging with 194

powerful navigation technology and is a versatile and multi-functional adjunct. With experience 195

in US image acquisition and interpretation if can be a potentially useful tool for surgery of brain 196

tumors. 197

198

Acce

pted

Arti

cle

Page 12: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

10

199

200

Acce

pted

Arti

cle

Page 13: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

11

Bibliography 201

1. Nabavi A, McL. Black P, Gering DT, Westin CF, Mehta V, Pergolizzi RS Jr et al. Serial 202

intraoperative magnetic resonance imaging of brain shift. Neurosurgery 2001; 48(4):787–203

797; discussion 797-798. https://doi.org/10.1227/00006123-200104000-00019 204

2. Moiyadi A V. Objective assessment of intraoperative ultrasound in brain tumors. Acta 205

Neurochir (Wien) 2014; 156(4):703–704. https://doi.org/10.1007/s00701-014-2010-3 206

3. Moiyadi A, Shetty P . Objective assessment of utility of intraoperative ultrasound in 207

resection of central nervous system tumors: A cost-effective tool for intraoperative 208

navigation in neurosurgery. J Neurosci Rural Pract 2011; 2 (1):4–11. 209

https://doi.org/10.4103/0976-3147.80077 210

4. Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C et al . Extent of 211

resection in patients with glioblastoma: Limiting factors, Perception of resectability, and 212

effect on survival. J Neurosurg 2012; 117(5):851–859. 213

https://doi.org/10.3171/2012.8.JNS12234 214

5. Eljamel MS, Mahboob SO . The effectiveness and cost-effectiveness of intraoperative 215

imaging in high-grade glioma resection; a comparative review of intraoperative ALA, 216

fluorescein, ultrasound and MRI. Photodiagnosis Photodyn Ther 2016; 16:35–43. 217

https://doi.org/10.1016/j.pdpdt.2016.07.012 218

6. Prada F, Del Bene M, Mattei L, Casali C, Filippini A, Legnani F et al. Fusion imaging for 219

intra-operative ultrasound-based navigation in neurosurgery. J Ultrasound 2017; 220

17(3):243–251. https://doi.org/10.1007/s40477-014-0111-8 221

Acce

pted

Arti

cle

Page 14: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

12

7. Renovanz M., A.-K. H, Henkel C., Nadji-Ohl M, Hopf NJ . Navigated versus non-222

navigated intraoperative ultrasound: Is there any impact on the extent of resection of high-223

grade gliomas? A retrospective clinical analysis. J Neurol Surgery, Part A Cent Eur 224

Neurosurg 2014; 75(3):224–230 225

8. Moiyadi A V., Shetty P . Direct navigated 3D ultrasound for resection of brain tumors: A 226

useful tool for intraoperative image guidance. Neurosurg Focus 2016; 40(3):1–8. 227

https://doi.org/10.3171/2015.12.FOCUS15529 228

9. Moiyadi A V. Intraoperative Ultrasound Technology in Neuro-Oncology Practice—229

Current Role and Future Applications. World Neurosurg 2016; 93:81–93. 230

https://doi.org/10.1016/j.wneu.2016.05.083 231

10. Patil AD, Singh V, Sukumar V, et al . Comparison of outcomes of free-hand 2-232

dimensional ultrasound-guided versus navigated 3-dimensional ultrasoundguided biopsy 233

for supratentorial tumours: A single-institution experience with 125 cases. 234

Ultrasonography 2019; 38(3):255–263. https://doi.org/10.14366/usg.18036 235

11. Moiyadi A V., Shetty P, John R. Non-enhancing gliomas: Does intraoperative 236

ultrasonography improve resections? Ultrasonography 2019; 38(2):156–165. 237

https://doi.org/10.14366/USG.18032 238

12. Moiyadi A V., Shetty PM, Mahajan A, Shetty PM, Moiyadi AV. Usefulness of three-239

dimensional navigable intraoperative ultrasound in resection of brain tumors with a 240

special emphasis on malignant gliomas. Acta Neurochir (Wien) 2013; 155(12):2217–2225. 241

https://doi.org/10.1007/s00701-013-1881-z 242

13. Moiyadi A V., Kannan S, Shetty P. Navigated intraoperative ultrasound for resection of 243

Acce

pted

Arti

cle

Page 15: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

13

gliomas: Predictive value, influence on resection and survival. Neurol India 2015; 244

63(5):727–735. https://doi.org/10.4103/0028-3886.166549 245

14. Dubey S, Janu A, Chaudhari S, Moiyadi A . Navigable 3D-Ultrasound Facilitates Supra-246

Radical Resections beyond the Contrast-Enhancing Boundaries in Malignant Gliomas. J 247

Neurol Surgery, Part A Cent Eur Neurosurg 2016; 77(04):372–375. 248

https://doi.org/10.1055/s-0035-1570005 249

15. Mahboob S, McPhillips R, Qiu Z, Jiang Y, Meggs C, Schiavone G . Intraoperative 250

Ultrasound-Guided Resection of Gliomas: A Meta-Analysis and Review of the Literature. 251

World Neurosurg 2016; 92:255–263. https://doi.org/10.1016/j.wneu.2016.05.007 252

16. Trevisi G, Barbone P., Treglia G., et al . Reliability of intraoperative ultrasound in 253

detecting tumor residual after brain diffuse glioma surgery: a systematic review and meta-254

analysis. Neurosurg Rev. 2019; https://doi.org/10.1007/s10143-019-01160-x 255

17. Selbekk T, Jakola AS, Solheim O, et al () Ultrasound imaging in neurosurgery: 256

Approaches to minimize surgically induced image artefacts for improved resection control. 257

Acta Neurochir (Wien) 2013; 155(6):973–980. https://doi.org/10.1007/s00701-013-1647-7 258

18. Trevisi G, Barbone P, Treglia G, Mattoli MV, Mangiola A. Reliability of intraoperative 259

ultrasound in detecting tumor residual after brain diffuse glioma surgery: a systematic 260

review and meta-analysis. Neurosurg Rev. Published online August 14, 2019. 261

doi:10.1007/s10143-019-01160-x 262

19. Zhang G, Li Z, Si D, Shen L. Diagnostic ability of intraoperative ultrasound for 263

identifying tumor residual in glioma surgery operation. Oncotarget. 2017;8(42):73105-264

73114. doi:10.18632/oncotarget.20394 265

Acce

pted

Arti

cle

Page 16: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

14

266

267

Acce

pted

Arti

cle

Page 17: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

15

Figure Captions 268

Figure 1. Operation theatre layout (a) – note the position of the US scanner in relation to the 269

navigation system and its proximity to the operating filed. Covering the control panel with a 270

sterile drape (b) allows direct control by the surgeon. 271

Figure 2. Navigated Ultrasound – (a) the probe which we use for performing nUS. (b) Localizer 272

with reflective spheres is fixed in a predetermined position onto the US probe. This is calibrated 273

to the navigation system allowing the US images to be registered in the same frame of reference 274

as the MRI scans previously registered on the navigation. 275

Figure 3. Positioning of the patient during US-guided surgery. It is essential to plan the position 276

in such a way that the conditions can be optimized for performing a post-resection scan bearing 277

in mind to have a cavity which can contain saline to allow a good acoustic coupling. The aim is 278

to keep the operating surface as flat (parallel to the floor) as is possible. (a) a right frontal 279

craniotomy and (b) a right paramedian suboccipital craniotomy. With careful planning an 280

optimal US scan can be obtained for virtually any cranial exposure. 281

Figure 4. 2D ultrasound – The same lesion is insonated with 2 different probes – (a) a high 282

frequency linear, 6-15MHz hockey-stick probe providing exquisite anatomical details of the 283

superficially located tumor with poorer delineation of deeper structural details; (b) a curvilinear, 284

5-13MHz probe showing a panoramic view which aids in the image orientation also.[high 285

resolution imgaes of both the US probe images are available in supplementary material 2 and 3 286

respectively] 287

Acce

pted

Arti

cle

Page 18: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

16

Figure 5. 2D ultrasound – (a) attempting to obtain a true axial image in the ultrasound (b). 288

Corresponding MR image in (c). It may not always be feasible to obtain such true anatomical 289

planes depending on the craniotomy aperture and location. 290

Figure 6. Navigated 2DUS - Screenshot of the real-time navigated 2D ultrasound from the 291

navigation system. The right panel shows the actual US image superimposed on the 292

corresponding MR plane. This screen is “live” and depicts the real-time moving US image as one 293

sweeps the operative field, exactly duplicating the US scanner screen. The left panel shows the 294

plane of insonation represented in the conventional axial, coronal, sagittal MRI images. Note that 295

the plane of insonation is not in a true anatomical plane as is the case in most surgical procedures. 296

Tumor which appears hypointense on the T1 MRI images and hyperechoic on US is outlined 297

with white dashed line. 298

Figure 7. Using Navigated 2D US to align the real-time 2D US image in a true anatomical plane. 299

(a) True Sagittal image and (b) True coronal image; in a case of left frontal high-grade glioma. 300

Figure 8. Navigated 3D Ultrasound – Screenshot after acquiring the 3DUS in the same case as 301

Figure VII. Using the navigator tool (depicted virtually as the green line with cross hairs) the US 302

images can now be seen in all 3 conventional ACS planes along with the corresponding MR 303

images. This screen layout can be customized in multiple display formats. 304

Figure 9. MR-US image fusion: Functional information can be outlined on the MR images. In 305

(a) Motor cortex in orange, corticospinal tracts in blue and the tumor itself in red have been 306

segmented. In (b), the inferior fronto-occipital tract has been outlined in green and co-displayed 307

with the US images. 308

Acce

pted

Arti

cle

Page 19: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

17

Figure 10. Brain-shift demonstrable on the nUS. Screenshot from the navigation system shows 309

the tumor segmented in red based on MRI images. Motor cortex is depicted in orange. Bottom 310

panel centre image shows the US image and the tumor now segmented in blue overlapping with 311

the MR segmented tumor (red). Shift is calculated manually in different directions and is 312

appreciably variable in all of them. Importantly this information can be used to infer the new 313

position of the motor cortex even if the US cannot define the motor cortex itself. 314

Figure 11. Resection control scans using serial real-time 2D grey scale US images. (a) Pre-315

resection (b) Intermediate, and (c) Post-resection imaging. Note the good image resolution of the 316

tumor mass as well as the surrounding anatomical details. However, also note that each of the 317

images is in a different 2D plane, thereby making direct comparison with the preceding images 318

challenging. 319

Figure 12. Resection Control Scans using n2DUS vs n3DUS - Left column depicts serially 320

acquired n2DUS images (a-c). Note the differing planes of each 2DUS as shown in the 321

corresponding MR cuts. In the same patient, (d) after acquiring a 3DUS, serial scans can be 322

depicted side-by-side and visualized in the same planes allowing easier comparison. 323

Figure 13. Navigated 3DUS (n3DUS) showing preoperative MRI (upper row), pre-resection US 324

(middle) and post-resection US images (bottom row). 325

Figure 14. Demonstration of progressive brain shift – Top row shows the pre-resection 3DUS in 326

ACS views. The tumor is outlined in orange. Middle row shows the same US superimposed on 327

the preoperative MRI. The brain-shift is obvious. Bottom row shows the pre-resection US 328

segmented tumor and the post-resection updated 3DUS showing the cavity which is displaced in 329

all three planes with respect to the pre-resection US. 330

Acce

pted

Arti

cle

Page 20: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

18

Figure 15. In-line views. Left insular glioma. Orthogonal inline views of MR are on leftmost 331

column. Central column shows coregistered pre-resection orthogonal US images and the right-332

most column is the post-resection US images in the same orthogonal planes. The vertical green 333

line corresponds to the direction of the surgeon’s operative field of view. Tumor which appears 334

hyperechoic on US is outlined with white dashed line in the pre-resection (central panel) as well 335

as post-resection (right panel). Note the residual tumor seen along with posterior enhancement 336

artefacts in the right panel. 337

338

Figure 16. Multimodal US-based intraoperative image guidance. Clockwise starting from the top 339

left corner (Navigation) till the bottom left corner (navigated 3-D US) there is an incremental 340

benefit of the US. The benefits (green boxes) and limitations (orange boxes) of each of the 341

modalities is highlighted. (IOMR- intraoperative MR Imaging). 342

343

344

Acce

pted

Arti

cle

Page 21: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 1

Operation theatre layout (a) – note the position of the US scanner in relation to the navigation system and its proximity to the

operating filed. Covering the control panel with a sterile drape (b) allows direct control by the surgeon

Acce

pted

Arti

cle

Page 22: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 2

Navigated Ultrasound – (a) the probe which we use for performing nUS. (b) Localizer with reflective spheres is fixed in a

predetermined position onto the US probe. This is calibrated to the navigation system allowing the US images to be registered

in the same frame of reference as the MRI scans previously registered on the navigation.

Acce

pted

Arti

cle

Page 23: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 3

Positioning of the patient during US-guided surgery. It is essential to plan the position in such a way that the conditions can be

optimized for performing a post-resection scan bearing in mind to have a cavity which can contain saline to allow a good

acoustic coupling. The aim is to keep the operating surface as flat (parallel to the floor) as is possible. (a) a right frontal

craniotomy and (b) a right paramedian suboccipital craniotomy. With careful planning an optimal US scan can be obtained for

virtually any cranial exposure.

Acce

pted

Arti

cle

Page 24: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 4

2D ultrasound – The same lesion is insonated with 2 different probes – (a) a high frequency linear, 6-15MHz hockey-stick probe

providing exquisite anatomical details of the superficially located tumor with poorer delineation of deeper structural details; (b)

a curvilinear, 5-13MHz probe showing a panoramic view which aids in the image orientation also.

Acce

pted

Arti

cle

Page 25: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 5

2D ultrasound – (a) attempting to obtain a true axial image in the ultrasound (b). Corresponding MR image in (c). It may not

always be feasible to obtain such true anatomical planes depending on the craniotomy aperture and location.

Acce

pted

Arti

cle

Page 26: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 6

. Navigated 2DUS - Screenshot of the real-time navigated 2D ultrasound from the navigation system. The right panel shows the

actual US image superimposed on the corresponding MR plane. This screen is “live” and depicts the real-time moving US image

as one sweeps the operative field, exactly duplicating the US scanner screen. The left panel shows the plane of insonation

represented in the conventional axial, coronal, sagittal MRI images. Note that the plane of insonation is not in a true anatomical

plane as is the case in most surgical procedures. Tumor which appears hypointense on the T1 MRI images and hyperechoic on

US is outlined with white dashed line.

Acce

pted

Arti

cle

Page 27: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 7

Using Navigated 2D US to align the real-time 2D US image in a true anatomical plane. (a) True Sagittal image and (b) True

coronal image; in a case of left frontal high-grade glioma.

Acce

pted

Arti

cle

Page 28: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 8

Navigated 3D Ultrasound – Screenshot after acquiring the 3DUS in the same case as Figure VII. Using the navigator tool

(depicted virtually as the green line with cross hairs) the US images can now be seen in all 3 conventional ACS planes along

with the corresponding MR images. This screen layout can be customized in multiple display formats.

Acce

pted

Arti

cle

Page 29: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 9

MR-US image fusion: Functional information can be outlined on the MR images. In (a) Motor cortex in orange, corticospinal

tracts in blue and the tumor itself in red have been segmented. In (b), the inferior fronto-occipital tract has been outlined in

green and co-displayed with the US images

Acce

pted

Arti

cle

Page 30: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 10

Brain-shift demonstrable on the nUS. Screenshot from the navigation system shows the tumor segmented in red based on MRI

images. Motor cortex is depicted in orange. Bottom panel centre image shows the US image and the tumor now segmented in

blue overlapping with the MR segmented tumor (red). Shift is calculated manually in different directions and is appreciably

variable in all of them. Importantly this information can be used to infer the new position of the motor cortex even if the US

cannot define the motor cortex itself.

Acce

pted

Arti

cle

Page 31: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 11

Resection control scans using serial real-time 2D grey scale US images. (a) Pre-resection (b) Intermediate, and (c) Post-

resection imaging. Note the good image resolution of the tumor mass as well as the surrounding anatomical details. However,

also note that each of the images is in a different 2D plane, thereby making direct comparison with the preceding images

challenging

Acce

pted

Arti

cle

Page 32: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 12

Resection Control Scans using n2DUS vs n3DUS - Left column depicts serially acquired n2DUS images (a-c). Note the differing

planes of each 2DUS as shown in the corresponding MR cuts. In the same patient, (d) after acquiring a 3DUS, serial scans can

be depicted side-by-side and visualized in the same planes allowing easier comparison.

Acce

pted

Arti

cle

Page 33: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 13

Navigated 3DUS (n3DUS) showing preoperative MRI (upper row), pre-resection US (middle) and post-resection US images

(bottom row).

Acce

pted

Arti

cle

Page 34: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 14

Demonstration of progressive brain shift – Top row shows the pre-resection 3DUS in ACS views. The tumor is outlined in

orange. Middle row shows the same US superimposed on the preoperative MRI. The brain-shift is obvious. Bottom row shows

the pre-resection US segmented tumor and the post-resection updated 3DUS showing the cavity which is displaced in all three

planes with respect to the pre-resection US.

Acce

pted

Arti

cle

Page 35: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Figure 15

In-line views. Left insular glioma. Orthogonal inline views of MR are on leftmost column. Central column shows coregistered

pre-resection orthogonal US images and the right-most column is the post-resection US images in the same orthogonal planes.

The vertical green line corresponds to the direction of the surgeon’s operative field of view. Tumor which appears hyperechoic

on US is outlined with white dashed line in the pre-resection (central panel) as well as post-resection (right panel). Note the

residual tumor seen along with posterior enhancement artefacts in the right panel.

Acce

pted

Arti

cle

Page 36: Accepted Article · 2020-06-17 · preoperatively acquired CT or MR images, is limited by23 the problem of brain-shift and 24 deformation (once dura is opened and brain is manipulated)

Fig 16

Multimodal US-based intraoperative image guidance. Clockwise starting from the top left corner (Navigation) till the bottom left

corner (navigated 3-D US) there is an incremental benefit of the US. The benefits (green boxes) and limitations (orange boxes)

of each of the modalities is highlighted.

Acce

pted

Arti

cle