We would like to thank the radiology technicians and nurses&#8217;staff of the Neuroradiology Area, IRCCS Istituto delle Scienze Neurologiche di Bologna, and their Coordinator Dr. Maria Grazia Crepaldi, for their collaboration.

The protocol is following the Local Research Committee&#39;s ethical standards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
1. Selection of the patients
<ol>
	<li>Adopt the following inclusion criteria: patients older than 18 years old, fully collaborating, presenting a tumor of the skull base, or pituitary-diencephalic region.</li>
	<li>Exclude patients with contraindication to MRI (i.e., a pacemaker or ferromagnetic material) or presenting with emergent clinical conditions (i.e., intracranial hypertension, the acute visual loss that requires immediate surgery), or pregnant women, or patients with mental illness, or those who explicitly refuse to participate in this protocol.</li>
</ol>
2. Preparation for the MRI exam
<ol>
	<li>Before the MRI exam, administer the safety form to exclude significant contraindication to the exam and contrast agent injection: no ferromagnetic materials in the body, evaluation of MRI devices, safe or conditional, no pacemaker, no eye contact lenses on.</li>
	<li>If the scanner used for the MRI acquisition is a high field (e.g., 3 T, see Table of Materials), consider any potential additional contraindications related, for example, to neurostimulation devices.</li>
	<li>Check whether the patient has claustrophobia.</li>
	<li>Ensure that the patient has read and signed the MRI consent form to acknowledge the imaging exam&#39;s risks and benefits.</li>
	<li>Have a neuropsychologist perform a general evaluation and a targeted neurocognitive assessment based on the tumor location.</li>
	<li>Administer the Edinburgh inventory to evaluate handedness dominance29.</li>
</ol>
3.&#160;Positioning of the patient in the scanner
<ol>
	<li>Give earplugs to the patient to reduce MRI noise.</li>
	<li>Head movements can affect imaging quality; thus, use foam pads to reduce head movements, immobilizing the head inside the MRI coil.</li>
	<li>Provide an emergency alarm button to the patient in case of need to interrupt the exam.</li>
	<li>Switch on the camera and microphone inside the scanner to monitor, speak, and listen to the patient from the MRI acquisition room outside the scanner.</li>
</ol>
4. Brain MRI protocol setting and acquisition parameters
<ol>
	<li>Acquire a standardized multimodal MRI protocol high-field scanner (1.5 T or 3T). The following sequence parameters refer to a 3 T MRI, using a head-neck high-density array coil (64 channels).</li>
	<li>Acquire high-resolution and volumetric anatomical sequences: T1-weighted pre- and post-gadolinium contrast agent administration and FLAIR T2-weighted.</li>
	<li>For T1 and T2 weighted images acquire continuous sagittal slices providing isotropic resolution of 1x1x1 mm3 scanning time of about 5 min per sequence.</li>
	<li>Acquire a high-resolution T2-weighted sequence and localize the tumor area for cranial nerve visualization: a volumetric CISS (Constructive Interference in Steady State) with voxel dimension of 0.5x0.5x0.5 mm3 (scanning time of about 9 minutes).</li>
	<li>Acquire diffusion-weighted sequences using single-shot echo-planar images (EPI), voxel dimension of 2x2x2 mm3, 64 magnetic gradient directions with b-value of 2000 s/mm2, echo time of 98 ms, and relaxation time of 4300 ms.</li>
	<li>Acquire five volumes with null b-value at the beginning of the diffusion-weighted acquisition with phase encoding direction set to anterior-posterior (for diffusion weighted images total scanning time of 5 minutes).</li>
	<li>Additionally, acquire three volumes with null b-value but reversed phase encoding direction, posterior-anterior, to correct imaging distortions due to the EPI acquisition (scanning time of 42 seconds). Continuous near-axial slices are acquired.</li>
	<li>Acquire additional sequences to investigate specific tumor features, such as multi- or single-voxel MRI-spectroscopy localized in the tumor area. 
	&#8203;NOTE: The total scanning time duration is about 30 minutes, excluding patient preparation for the MRI exam.</li>
</ol>
5. Brain MR images pre-processing
<ol>
	<li>Convert the MRI data from the imaging format adopted by MRI acquisition consoles, DICOM (.dcm), to the NIFTI format (.nii) used in advanced imaging analyses.</li>
	<li>Run the dcm2niix function (https://github.com/rordenlab/dcm2niix). Set as input files dicom images and as output the corresponding .nii files: T1.nii, Flair.nii, T1_contrast.nii, DTI_b2000.nii and DTI_b0_flip.nii.</li>
	<li>Install the FSL (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki) and MRtrix3 (https://www.mrtrix.org) software needed for the advanced imaging analyses.</li>
	<li>Register the Flair.nii and T1_contrast.nii to the T1.nii image by running the FSL-flirt function, which performs a linear image registration.</li>
	<li>Register the DTI_b2000.nii image to the T1.nii by running the FSL-epi_reg function, which takes into account EPI imaging distortion artifacts.</li>
	<li>Run the FSL-topup function to correct phase encoding direction artifacts presenting the DTI_b2000.nii image. Set the DTI_b0_flip.nii inverse phase encoding acquisition as the &#34;in_main&#34; input file.</li>
	<li>Run the MRtrix3-dwidenoise function for imaging denoising with a principal component noise modeling.</li>
	<li>To correct eddy current and signal drop-out artifact, run the FSL-eddy function, and for MRI coil-induced signal inhomogeneities, the MRtrix3-dwibias correct function.</li>
	<li>Run the FSL-bet function to remove the scalp signal presenting the T1.nii image and rename the output file by using the &#34;_brain&#34; suffix: T1_brain.nii.</li>
</ol>
6. Tumor segmentation
<ol>
	<li>Install the itk-snap software (http://www.itksnap.org)&#160;30.</li>
	<li>Once the itk-snap software is installed, press File - Open Main Image and select the T1.nii image, then press File - Add Another Imager and upload the Flair.nii and T1_contrast.nii images, setting the semi-transparent overlay option.</li>
	<li>Inspect the tumor in the T1.nii, Flair.nii, and T1_contrast.nii images. Choose the anatomical plane to follow when drawing the lesion, e.g., axial.</li>
	<li>Place the pointer in one axial slice to start. In the Main Toolbar, select the Polygon Inspector icon and start drawing tumor boundaries by using the Freehand Drawing Style - Smooth curve or Polygon.</li>
	<li>Once finished drawing the tumor perimeter, close the curve linking the first and last dots, press Accept, and continue drawing in the next slice. For large tumor lesions, to accelerate the drawing process, skip some axial slices (e.g., three), and draw the lesion perimeter in interleaved slices.</li>
	<li>At the end of the lesion perimeter drawing, select Tools - Interpolate Labels, set the Label to/with interpolate as the tumor lesion and the Interpolate along a single axis as the axis orientation followed in drawing the tumor boundaries.</li>
	<li>Select Segmentation - Save Segmentation Image and name the tumor segmentation as Tumor_mask.nii by selecting the Nifti format option to save.</li>
</ol>
7. Tractography analysis
<ol>
	<li>Run the FSL-dtifit function to model diffusivity and the different spatial directions and obtain the following diffusion tensor maps: FA.nii, MD.nii, and V1.nii. Evaluate these DTI maps to access abnormal diffusivity values that may occur in the presence of tumor edema or infiltration.</li>
	<li>Run the MRtrix3-tckgen function with the default setting &#34;ifod2&#34; to perform probabilistic tractography and reconstruct the white matter pathways by modeling crossing-fibers issues31.</li>
	<li>Adopt a seed-target approach by setting the &#34;-seed_image&#34; and &#34;-include&#34; options based on a priori anatomical knowledge.</li>
	<li>Manually draw regions of interest (ROIs) set as seed or target for tractography. Alternatively, use atlas-based ROIs. See Mormina et at.32 for the optic radiation tractography, Hales et al.33 for the optic chiasm and optic cranial nerves, and Testa et al.34 for the pyramidal tracts.</li>
	<li>Launch the FSL-fsleyes image viewer, select Open, and choose images to inspect visually.</li>
	<li>In the FSL- fsleyes viewer, go to Setting - Ortho View 1 and activate the Edit Mode tool.</li>
	<li>Click the FSL-fsleyes pencil icon and draw the tractography ROIs.</li>
	<li>Install the Freesurfer (https://surfer.nmr.mgh.harvard.edu) software.</li>
	<li>Run the Freesurfer-Recon-all function on the T1.nii image to obtain the automatic cortical region segmentation to use as tractography ROIs.</li>
	<li>Run the FSL-epi_regregistration function, setting as input image the T1.nii, and reference image the DTI_b2000.nii, save the registration output matrix (T1_onto_DTI.mat).</li>
	<li>Use the obtained T1_onto_DTI.mat matrix to register the segmented ROIs to the DTI_b2000.nii image.</li>
	<li>Run the tractography using the MRtrix3-tckgen function.</li>
	<li>Run the MRtrix3-tckmap function to convert the &#34;.tck&#34; streamlines tractography output in the &#34;-template FA.nii&#34; image.</li>
	<li>Run the FSL-flirt function to linearly register the T1.nii image to the MNI152_T1_2mm_brain.nii template.</li>
	<li>Save the output matrix as T1_onto_MNI.mat. Run the FSL-convert_xfm function setting the &#34;-concat&#34; option as T1_onto_MNI.mat and T1_onto_DTI.mat, save the output matrix as DTI_onto_MNI.mat.</li>
</ol>
8. Tractography: along-tract analysis
<ol>
	<li>For an accurate description of DTI parameters, use along-tract algorithms, such as the Matlab-based algorithm that models the surface tract geometry with the Laplacian operator properties35.</li>
	<li>Install the Matlab software (https://matlab.mathworks.com) and request the along-tract code to the developing authors35.</li>
	<li>Alternatively, use the MRtrix3-tcksample function for along-tract analysis as Matlab requires a license.</li>
</ol>
9. 3D-rendering visualization
<ol>
	<li>Install the Surf Ice software (https://www.nitrc.org/plugins/mwiki/index.php/surfice:MainPage).</li>
	<li>In the Surf Ice command panel, click on Advanced - Convert voxelwise to mesh, select the nifti image to convert, save the resulting .obj file.</li>
	<li>In the Surf Ice command panel, click File - Open, and select the .obj file to visualize the 3D volume rendering.</li>
</ol>
10. Preoperative clinical examinations
<ol>
	<li>Perform bio-humoral endocrinological assessment, consisting of prolactin, TSH, freeT4, ACTH, cortisol, GH, LH, FSH, and serum tests total testosterone/estradiol, respectively in men and women.</li>
	<li>Analyze the 24-hour urine volume and serum and urine osmolality and sodium levels to determine the presence of diabetes insipidus.</li>
	<li>Perform an ophthalmological evaluation, including visual acuity measurement, computerized visual field assessment, and retinal optical coherence tomography (OCT).</li>
	<li>Perform a neurological physical examination, with a collection of anamnestic information about weight gain, the sensation of hunger, continuously monitoring rectal temperature every 2 min for 24 h using a portable device to evaluate the circadian temperature rhythm, and 24 h sleep-wake cycle recording (including an electroencephalogram, right and left electro-oculogram, electrocardiogram, and electromyogram of mylohyoid and left and right tibialis muscles)36,37,38.</li>
</ol>
11. Surgical planning
<ol>
	<li>Discuss in a collegial team meeting each patient candidate to surgery, based on the results of tumor segmentation and relationship with the functional eloquent neural structures (optic nerves and chiasm, pituitary stalk, third ventricle, internal carotid artery, anterior cerebral artery-anterior communicating artery (ACA-ACoA) complex, basilar artery, cranial nerves III, IV, VI, mammillary bodies, white matter tracts, and functional cortical areas) to determine the most appropriate surgical approach.</li>
	<li>Select the surgical corridor with the minimal risk of injuries of neural structures39.</li>
	<li>Define the safe resection area for each case, localizing the critical neural structure (such as chiasm, mammillary body) under whose proximity the resection must be arrested to avoid permanent damage39.</li>
	<li>Merge the most relevant MRI sequences and import them into the operative phase&#39;s neuronavigation system.</li>
</ol>
12. Surgery preparation
<ol>
	<li>Induce general anesthesia adopting total intravenous anesthesia with propofol and remifentanil (it has been demonstrated that the other anesthetic agents are among the most critical factors affecting intraoperative monitoring reliability, increasing the false-negative rate), avoiding myorelaxant40.</li>
	<li>Perform oro-tracheal intubation with gauzes in the oropharynx to prevent blood or fluid leakage in the stomach or airways41.</li>
	<li>Set up the neurophysiological monitoring, with continuous recording of motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) and free-running electromyography (EMG) for cranial nerves.42</li>
	<li>Import the MRI data, including the tractography reconstructions, in the neuronavigation system (Table of Materials).</li>
	<li>Select the brain surgery electromagnetic registration modality on the neuronavigation system.</li>
	<li>Register the neuronavigation system on the patient, adopting a free-tracking technique or external markers.</li>
	<li>Control the accuracy of the achieved registration, checking the position of external markers (i.e., ear or nose) on the imported MRI; if the result is not acceptable, repeat the registration.</li>
	<li>Place the patient in a semi-sitting position; Mayfield&#39;s use to fix the head is not needed43.</li>
	<li>Administer corticosteroid (endovenous flebocortid, dosage depending on the patient&#39;s weight) and antibiotics (2 g of amoxicillin-clavulanic acid)44.</li>
</ol>
13. Endoscopic endonasal surgery
<ol>
	<li>Start with a 0&#176; endoscope (Table of Materials).</li>
	<li>Harvest the naso-septal flap45.</li>
	<li>Perform an anterior sphenoidotomy, followed by posterior septostomy and ethmoidectomy with preservation of the middle turbinate, when possible43.</li>
	<li>Open the sellar and tuberculum bone41.</li>
	<li>Incise the dura layer with an H-shape, after coagulation of the superior intercavernous sinus41.</li>
	<li>Cleave the tumor by the arachnoidal plane43.</li>
	<li>Centrally debulk the tumor43.</li>
	<li>Remove its capsule from the surrounding diencephalic neural structures, arresting the resection in case of tumor adhesion to eloquent structures visualized under neuronavigation guidance43.</li>
	<li>Explore the surgical cavity with angled optics (Table of Materials)46.</li>
	<li>Ensure hemostasis with bipolar coagulation or hemostatic agents.</li>
	<li>Close the osteo-meningeal opening with an intradural intracranial layer of dural substitute43.</li>
	<li>Place an extradural intracranial layer of dural substitute, scaffolded with abdominal fat and eventually bone (Table of Materials)43.</li>
	<li>Cover the closure with the naso-septal flap43.</li>
</ol>
14. Histological examination
<ol>
	<li>Fix tumor samples with 10% formalin and embed them in paraffin immediately after surgery.</li>
	<li>Cut tissue into sections of 4 &#181;m thickness and stain with hematoxylin and eosin. The histological diagnosis must be based on the most recent version of the WHO classification of brain tumors (2016)47.</li>
	<li>Perform specimen immunohistochemical staining by an automated immunohistochemical staining instrument, using avidin-biotin labeling and diaminobenzidine as a detection reagent. For craniopharyngiomas, adopt anti-beta-catenin, anti-BRAF v600E mutant epitope, and anti-Ki67 antibodies for immunohistochemical staining (Table of Materials).</li>
	<li>Evaluate the Ki-67 index through the manual count of positive tumor cells48.</li>
</ol>
15. Post-surgical patient management
<ol>
	<li>Wake the patient immediately after surgery.</li>
	<li>Restore spontaneous breathing from the mouth by filling nasal cavities with absorbable and non-absorbable material.</li>
	<li>Monitor vital parameters (blood pressure, heart rate, oxygen saturation and consciousness state) for the following 6-12 hours in ICU.</li>
	<li>Restore oral feeding after 12 hours.</li>
	<li>Perform a CT scan after 6-9 hours.</li>
	<li>Maintain bed rest for three days with heparin treatment.</li>
	<li>Control fluid balance every 12 hours and assess serum electrolytes every 24 hours.</li>
	<li>Administer corticosteroid therapy (endovenous flebocortid in the first 24 hours, and then oral cortone acetate 30 +15 mg/day).</li>
	<li>Perform an MRI with/without gadolinium within 72 hours after surgery.</li>
	<li>Discharge the patient on the 4th day.</li>
</ol>
16. Early follow-up
<ol>
	<li>Repeat the complete endocrinological assessment 30 days after surgery43.</li>
	<li>Repeat the ophthalmological assessment three months after surgery43.</li>
	<li>Repeat the neurological physical examination and temperature and sleep-wake rhythms function investigations three months after surgery46.</li>
	<li>Perform the MRI with/without gadolinium three months after surgery46.</li>
</ol>
17. Adjuvant therapy
<ol>
	<li>Evaluate the presence of early tumor progression, and if it is indicated, refer the patient to radiation therapy43.</li>
</ol>
18. Long-term follow-up
<ol>
	<li>Repeat the clinical, endocrinological, and ophthalmological assessments annually43.</li>
	<li>Perform yearly MRI with/without gadolinium: in case of recurrence, the patient can be re-operated on and then referred to radiation therapy or directly referred to radiotherapy43.</li>
</ol>

The authors have nothing to disclose

The application of the presented protocol resulted in a safe and effective treatment of one of the most challenging intracranial tumors such as a craniopharyngioma invading the 3rd ventricle, possibly opening up a new horizon for a lesion that was defined by H. Cushing about a century ago as the most baffling intracranial neoplasm1. The combination of accurate preoperative planning, integrating advanced MRI techniques, and multidisciplinary clinical assessments have permitted us to tail...

The possibility to approach the skull base midline and paramedian regions through an anterior route, adopting the nasal fossae as natural cavities, has a long history, dating back more than one century1. However, in the last 20 years, the visualization and operative technologies have improved enough to expand their possibility of including the treatment of the most complex tumors such as meningiomas, chordomas, chondrosarcomas, and craniopharyngiomas1 due to the (1) introduction of the endoscope, which gives a panoramic and detailed 2D/3D view of these regions to the surgeon, (2) the development of intraoperative neuronavigation systems, and (3) the implementation of dedicated surgical instruments. As painstakingly demonstrated by Kassam et al. and confirmed by multiple reviews and meta-analyses, the advantages of this surgical approach are mainly represented by its chances to resect challenging skull base tumors, avoiding any direct brain retraction or nerve manipulation, thus reducing the risk of surgical complications and long-term neurological and visual sequelae2,3,4,5,6,7,8,9,10,11,12.
For multiple skull base and pituitary-diencephalic tumors, the ideal surgical goal has changed in the last years from the most extensive tumor removal possible to the safest removal with preservation of the neurological functions to preserve the patient&#39;s quality of life3. This limitation could be compensated by innovative and effective adjuvant treatments, such as radiation therapy (adopting massive particles such as proton or carbon ions when appropriate) and, for selected neoplasms, by chemotherapy as inhibitors of the BRAF/MEK pathway for the craniopharyngiomas13,14,15.
However, to pursue these goals, a careful preoperative assessment is crucial, to tailor the surgical strategy to each case&#39;s specific feature2. In most centers, the MRI preoperative protocol is usually performed only with standard structural sequences, which provide the morphological characterization of the lesion. However, with these techniques it is not always possible to assess the anatomical relationship of the tumor with adjacent structures reliably3. Moreover, each patient may present different pathology-induced functional reorganization profiles detectable only with diffusion MRI tractography and functional MRI (fMRI), which can be used to provide guidance both in the surgery planning and in the intraoperative steps16,17.
Currently, fMRI is the most commonly used neuroimaging modality for mapping brain functional activity and connectivity, as guidance for surgical planning18,19 and to improve the patients&#39; outcome20. Task-based fMRI is the modality of choice to identify &#34;eloquent&#34; brain regions that are functionally involved in specific task performance (e.g., finger tapping, phonemic fluency), but is not applicable for the study of skull base tumors.
Diffusion MRI tractography permits in vivo and noninvasive reconstruction of white matter brain connections as well as cranial nerves, investigating the brain hodological structure21. Different tractography algorithms have been developed to reconstruct axonal pathways by linking water molecule diffusivity profiles, evaluated within each brain voxel. Deterministic tractography follows the dominant diffusivity direction, whereas probabilistic tractography evaluates possible pathways&#39; connectivity distribution. Additionally, different models can be applied to evaluate diffusivity within each voxel, and it is possible to define two main categories: single fiber models, such as the diffusion tensor model, where a single fiber orientation is evaluated, and multiple-fiber models, such as spherical deconvolution, where several crossing-fiber orientations are reconstructed22,23. Despite the methodological debate about diffusion MRI tractography, its utility in the neurosurgical workflow is currently established. It is possible to evaluate white matter tract dislocation and distance to the tumor, preserving specific white matter connections. Moreover, diffusion tensor imaging (DTI) maps, especially fractional anisotropy (FA) and mean diffusivity (MD), can be applied to assess microstructural white matter alterations related to possible tumor infiltration and for longitudinal tract monitoring. All these features make diffusion MRI tractography a powerful tool both for pre-surgical planning and intra-operative decision making through neuronavigation systems24.
However, the application of tractography techniques to skull base surgery has been limited by the need for specialized technical knowledge and the time-consuming work-up to optimize diffusion MRI sequence acquisition, analysis protocol, and incorporating tractography results in neuronavigation systems25.Finally, further limitations are due to the technical difficulties extending these analyses from intraparenchymal to extra-parenchymal white matter structures, as cranial nerves. Indeed, only recent studies presented preliminary results attempting to integrate advanced MRI and skull base surgery26,27,28.
The present paper presents a protocol for the multidisciplinary management of pituitary-diencephalic and skull base tumors using diffusion MRI tractography. The implementation of this protocol in the institution resulted from the collaboration between neurosurgeons, neuro-endocrinologists and the neuroimaging team (including clinical and bioinformatics expertise) to offer an effective integrated multi-axial approach to these patients.
In the center, we have integrated multidisciplinary protocols for managing patients with skull base tumors, to provide the most informative description possible, and to tailor and personalize the surgical plan. We show that this protocol can be adopted both in the clinical and the research setting for any patient with a skull base tumor to guide the treatment strategy and to improve the knowledge on the brain modifications induced by these lesions.

<table><tbody><tr><td>BRAF V600E-specific clone VE1</td><td>Ventana</td><td></td><td></td></tr><tr><td>Dural Substitute</td><td>Biodesign, Cook Medical</td><td></td><td></td></tr><tr><td>Endoscope</td><td>Karl Storz, 4mm in diameter, 18 cm in length, Hopkins II &amp;ndash; Karl Storz Endoscopy</td><td></td><td></td></tr><tr><td>Immunohistochemical staining instrument&amp;nbsp;</td><td>Ventana Benchmark, Ventana Medical Systems</td><td></td><td></td></tr><tr><td>MRI</td><td>3T Magnetom Skyra, Siemens Health Care</td><td></td><td></td></tr><tr><td>Neuronavigator</td><td>Stealth Station S8 Surgical Navigation System, MEDTRONIC</td><td></td><td></td></tr></tbody></table>

role of diffusion mri tractography in endoscopic endonasal skull base surgery

Endoscopic endonasal surgery has gained a prominent role in the management of complex skull base tumors. It allows the resection of a large group of benign and malignant lesions through a natural anatomical extra-cranial pathway, represented by the nasal cavities, avoiding brain retraction and neurovascular manipulation. This is reflected by the patients' prompt clinical recovery and the low risk of permanent neurological sequelae, representing the main caveat of conventional skull base surgery. This surgery must be tailored to each specific case, considering its features and relationship with surrounding neural structures, mostly based on preoperative neuroimaging. Advanced MRI techniques, such as tractography, have been rarely adopted in skull base surgery due to technical issues: lengthy and complicated processes to generate reliable reconstructions for inclusion in the neuronavigation system. 
This paper aims to present the protocol implemented in the institution and highlights the synergistic collaboration and teamwork between neurosurgeons and the neuroimaging team (neurologists, neuroradiologists, neuropsychologists, physicists, and bioengineers) with the final goal of selecting the optimal treatment for each patient, improving the surgical results and pursuing the advancement of personalized medicine in this field.

A 55-year-old woman presented with progressive visual deficits. Her medical history was unremarkable. On ophthalmological evaluation, bilateral reduction of visual acuity (6/10 in the right eye and 8/10 in the left eye) was revealed, and the computerized visual field showed complete bitemporal hemianopia. No further deficits were evident on neurological examination, but the patient reported persistent asthenia and an increase in hunger and thirst sensation in the previous 2-3 months, with...

Watch this Scientific Journal Video about Role of Diffusion MRI Tractography in Endoscopic Endonasal Skull Base Surgery at JoVE.com

Role of Diffusion MRI Tractography in Endoscopic Endonasal Skull Base Surgery

We present a protocol to integrate diffusion MRI tractography in patient work-up to endoscopic endonasal surgery for a skull base tumor. The methods for adopting these neuroimaging studies in the pre- and intra-operative phases are described.

Endoscopic endonasal surgery has gained a prominent role in the management of complex skull base tumors. It allows the resection of a large group of ...

role-diffusion-mri-tractography-endoscopic-endonasal-skull-base

Research

JoVE Journal

Neuroscience

3.5K Views.  Center for the Diagnosis and Treatment of Hypothalamic-Pituitary Diseases - Pituitary Unit. Met behulp van een geïntegreerd neuroimaging- en neurochirurgieprotocol is het mogelijk om verschillende expertises samen te voegen in een synergetisch kader om een patiëntspecifieke tumorresectiechirurgie op maat te maken. Met behulp van MRI-tractografie is het mogelijk om dislocatie van de witte stof en tumorafstand te visualiseren. De veelzijdigheid ervan in glioomchirurgie is vastgesteld en kan ook worden toegepast bij medicijnresistente focale epilepsie.De integratie van geavanc...

Video: Role of Diffusion MRI Tractography in Endoscopic Endonasal Skull Base Surgery

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when studying the brain, as the functional role that a brain area fulfills may be largely defined by its connections to other brain areas. In this report, we describe a novel, non-invasive approach for relating brain structure and function using magnetic resonance imaging (MRI). This approach, a combination of structural imaging of long-range fiber connections and functional imaging data, is illustrated in two distinct cognitive domains, visual attention and face perception. Structural imaging is performed with diffusion-weighted imaging (DWI) and fiber tractography, which track the diffusion of water molecules along white-matter fiber tracts in the brain (Figure 1). By visualizing these fiber tracts, we are able to investigate the long-range connective architecture of the brain. The results compare favorably with one of the most widely-used techniques in DWI, diffusion tensor imaging (DTI). DTI is unable to resolve complex configurations of fiber tracts, limiting its utility for constructing detailed, anatomically-informed models of brain function. In contrast, our analyses reproduce known neuroanatomy with precision and accuracy. This advantage is partly due to data acquisition procedures: while many DTI protocols measure diffusion in a small number of directions (e.g., 6 or 12), we employ a diffusion spectrum imaging (DSI)1, 2 protocol which assesses diffusion in 257 directions and at a range of magnetic gradient strengths. Moreover, DSI data allow us to use more sophisticated methods for reconstructing acquired data. In two experiments (visual attention and face perception), tractography reveals that co-active areas of the human brain are anatomically connected, supporting extant hypotheses that they form functional networks. DWI allows us to create a "circuit diagram" and reproduce it on an individual-subject basis, for the purpose of monitoring task-relevant brain activity in networks of interest.

We describe a novel approach for simultaneous analysis of brain function and structure using magnetic resonance imaging (MRI). We assess brain structure with high-resolution diffusion-weighted imaging and white-matter fiber tractography. Unlike standard structural MRI, these techniques allow us to directly relate anatomical connectivity to functional properties of brain networks.

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when ...

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls. 	
DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.	
In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.

Diffusion tensor imaging (DTI) basically serves as an MRI-based tool to identify in vivo the microstructure of the brain and pathological processes due to neurological disorders within the cerebral white matter. DTI-based analyses allow for application to brain diseases both at the group level and in single subject data.

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present ...

Medicine

DTI of the Visual Pathway - White Matter Tracts and Cerebral Lesions

DTI is a technique that identifies white matter tracts (WMT) non-invasively in healthy and non-healthy patients using diffusion measurements. Similar to visual pathways (VP), WMT are not visible with classical MRI or intra-operatively with microscope. DTI will help neurosurgeons to prevent destruction of the VP while removing lesions adjacent to this WMT. We have performed DTI on fifty patients before and after surgery between March 2012 to January 2014. To navigate we used a 3DT1-weighted sequence. Additionally, we performed a T2-weighted and DTI-sequences. The parameters used were, FOV: 200 x 200 mm, slice thickness: 2 mm, and acquisition matrix: 96 x 96 yielding nearly isotropic voxels of 2 x 2 x 2 mm. Axial MRI was carried out using a 32 gradient direction and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2 and b-value of 800 s/mm&#178;. The scanning time was less than 9 min.
The DTI-data obtained were processed using a FDA approved surgical navigation system program which uses a straightforward fiber-tracking approach known as fiber assignment by continuous tracking (FACT). This is based on the propagation of lines between regions of interest (ROI) which is defined by a physician. A maximum angle of 50, FA start value of 0.10 and ADC stop value of 0.20 mm&#178;/s were the parameters used for tractography.
There are some limitations to this technique. The limited acquisition time frame enforces trade-offs in the image quality. Another important point not to be neglected is the brain shift during surgery. As for the latter intra-operative MRI might be helpful. Furthermore the risk of false positive or false negative tracts needs to be taken into account which might compromise the final results.

Diffusion tensor imaging (DTI) was performed to try to depict the major parts of the visual pathway. The goal was to use an FDA approved standard commercial workstation which could be used for everyday routine in order to try to reduce postoperative damage of the visual pathway in the patients.

DTI is a technique that identifies white matter tracts (WMT) non-invasively in healthy and non-healthy patients using diffusion measurements. Similar to ...

Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography

In albinism, the number of ipsilaterally projecting retinal ganglion cells (RGCs) is significantly reduced. The retina and optic chiasm have been proposed as candidate sites for misrouting. Since a correlation between the number of lateral geniculate nucleus (LGN) relay neurons and LGN size has been shown, and based on previously reported reductions in LGN volumes in human albinism, we suggest that fiber projections from LGN to the primary visual cortex (V1) are also reduced. Studying structural differences in the visual system of albinism can improve the understanding of the mechanism of misrouting and subsequent clinical applications. Diffusion data and tractography are useful for mapping the OR (optic radiation). This manuscript describes two algorithms for OR reconstruction in order to compare brain connectivity in albinism and controls.An MRI scanner with a 32-channel head coil was used to acquire structural scans. A T1-weighted 3D-MPRAGE sequence with 1 mm3 isotropic voxel size was used to generate high-resolution images for V1 segmentation. Multiple proton density (PD) weighted images were acquired coronally for right and left LGN localization. Diffusion tensor imaging (DTI) scans were acquired with 64 diffusion directions. Both deterministic and probabilistic tracking methods were run and compared, with LGN as the seed mask and V1 as the target mask. Though DTI provides relatively poor spatial resolution, and accurate delineation of OR may be challenging due to its low fiber density, tractography has been shown to be advantageous both in research and clinically. Tract based spatial statistics (TBSS) revealed areas of significantly reduced white matter integrity within the OR in patients with albinism compared to controls. Pairwise comparisons revealed a significant reduction in LGN to V1 connectivity in albinism compared to controls. Comparing both tracking algorithms revealed common findings, strengthening the reliability of the technique.

This manuscript describes deterministic and probabilistic algorithms for white matter (WM) reconstruction, used to examine differences in optic radiation (OR) connectivity between albinism and controls. Although probabilistic tractography follows the true course of nerve fibers more closely, deterministic tractography was run to compare the reliability and reproducibility of both techniques.

In albinism, the number of ipsilaterally projecting retinal ganglion cells (RGCs) is significantly reduced. The retina and optic chiasm have been proposed ...

Fiber Connections of the Supplementary Motor Area Revisited: Methodology of Fiber Dissection, DTI, and Three Dimensional Documentation

The purpose of this study is to show the methodology for the examination of the white matter connections of the supplementary motor area (SMA) complex (pre-SMA and SMA proper) using a combination of fiber dissection techniques on cadaveric specimens and magnetic resonance (MR) tractography. The protocol will also describe the procedure for a white matter dissection of a human brain, diffusion tensor tractography imaging, and three-dimensional documentation. The fiber dissections on human brains and the 3D documentation were performed at the University of Minnesota, Microsurgery and Neuroanatomy Laboratory, Department of Neurosurgery. Five postmortem human brain specimens and two whole heads were prepared in accordance with Klingler's method. Brain hemispheres were dissected step by step from lateral to medial and medial to lateral under an operating microscope, and 3D images were captured at every stage. All dissection results were supported by diffusion tensor imaging. Investigations on the connections in line with Meynert's fiber tract classification, including association fibers (short, superior longitudinal fasciculus I and frontal aslant tracts), projection fibers (corticospinal, claustrocortical, cingulum, and frontostriatal tracts), and commissural fibers (callosal fibers) were also conducted.

The purpose of this study is to show each step of the fiber dissection technique on human cadaveric brains, the 3D documentation of these dissections, and the diffusion tensor imaging of the anatomically dissected fiber pathways.

The purpose of this study is to show the methodology for the examination of the white matter connections of the supplementary motor area (SMA) complex ...

Endoscopic Endonasal Trans-sphenoidal Approach: Minimally Invasive Surgery for Pituitary Adenomas

Endoscopic endonasal trans-sphenoidal surgery has become the gold standard for the surgical treatment of pituitary adenomas and many other pituitary lesions. Refinements in surgical techniques, technological advancements, and incorporation of neuronavigation have rendered this surgery minimally invasive. The complication rates of this surgery are very low while excellent results are consistently obtained through this approach.
This paper focuses on the step-by-step surgical approach to pituitary adenomas, which is based on personal experience, and details the results obtained with this minimally invasive surgery.

The aim of this paper is to describe the different steps of the endoscopic endonasal approach to the sella turcica.

Endoscopic endonasal trans-sphenoidal surgery has become the gold standard for the surgical treatment of pituitary adenomas and many other pituitary ...

A MRI-Based Toolbox for Neurosurgical Planning in Nonhuman Primates

In this paper, we outline a method for surgical preparation that allows for the practical planning of a variety of neurosurgeries in NHPs solely using data extracted from magnetic resonance imaging (MRI). This protocol allows for the generation of 3D printed anatomically accurate physical models of the brain and skull, as well as an agarose gel model of the brain modeling some of the mechanical properties of the brain. These models can be extracted from MRI using brain extraction software for the model of the brain, and custom code for the model of the skull. The preparation protocol takes advantage of state-of-the-art 3D printing technology to make interfacing brains, skulls, and molds for gel brain models. The skull and brain models can be used to visualize brain tissue inside the skull with the addition of a craniotomy in the custom code, allowing for better preparation for surgeries directly involving the brain. The applications of these methods are designed for surgeries involved in neurological stimulation and recording as well as injection, but the versatility of the system allows for future expansion of the protocol, extraction techniques, and models to a wider scope of surgeries.

The method outlined below aims to provide a comprehensive protocol for the preparation of nonhuman primate (NHP) neurosurgery using a novel combination of three-dimensional (3D) printing methods and MRI data extraction.

In this paper, we outline a method for surgical preparation that allows for the practical planning of a variety of neurosurgeries in NHPs solely using ...

Bioengineering

Full Endoscopic Transforaminal Thoracic Discectomy Operative Technique

Thoracic disc herniations are a degenerative pathology of the thoracic spine wherein a portion of nucleus pulposis herniates into the epidural space, potentially causing spinal cord or nerve root compression. Traditional surgical treatment for patients with thoracic disc herniations requires relatively invasive anterior or posterolateral approaches that involve extensive muscular dissection and removal of bone in order to access and remove the disc herniation without causing undue compression of the spinal cord. Full endoscopic thoracic discectomy is a minimally invasive technique which allows for the resection of thoracic disc herniations through a small (1 cm) incision, minimizing collateral tissue trauma and obviating the need for the extensive muscle dissection and bony removal required for traditional surgical approaches. In this article, we describe in detail the operative technique for full endoscopic thoracic discectomy and discuss the pearls and pitfalls of the technique. We also provide a review of the outcomes and complications as seen in the literature.

This protocol demonstrates the surgical technique for full endoscopic transforaminal resection of thoracic disc herniations.

Thoracic disc herniations are a degenerative pathology of the thoracic spine wherein a portion of nucleus pulposis herniates into the epidural space, ...

Study Design for Navigated Repetitive Transcranial Magnetic Stimulation for Speech Cortical Mapping

The cortical areas involved in human speech should be characterized reliably prior to surgery for brain tumors or drug-resistant epilepsy. The functional mapping of language areas for surgical decision-making is usually done invasively by electrical direct cortical stimulation (DCS), which is used to identify the organization of the crucial cortical and subcortical structures within each patient. Accurate preoperative non-invasive mapping aids surgical planning, reduces time, costs, and risks in the operating room, and provides an alternative for patients not suitable for awake craniotomy. Non-invasive imaging methods like MRI, fMRI, MEG, and PET are currently applied in presurgical design and planning. Although anatomical and functional imaging can identify the brain regions involved in speech, they cannot determine whether these regions are critical for speech. Transcranial magnetic stimulation (TMS) non-invasively excites the cortical neuronal populations by means of electric field induction in the brain. When applied in its repetitive mode (rTMS) to stimulate a speech-related cortical site, it can produce speech-related errors analogous to those induced by intraoperative DCS. rTMS combined with neuronavigation (nrTMS) enables neurosurgeons to preoperatively assess where these errors occur and to plan the DCS and the operation to preserve the language function. A detailed protocol is provided here for non-invasive speech cortical mapping (SCM) using nrTMS. The proposed protocol can be modified to best fit the patient- and site-specific demands. It can also be applied to language cortical network studies in healthy subjects or in patients with diseases that are not amenable to surgery.

Navigated repetitive transcranial magnetic stimulation is a highly efficient non-invasive tool for mapping speech-related cortical areas. It helps in designing brain surgery and speeds up the direct cortical stimulation conducted during the surgery. This report describes how to perform speech cortical mapping reliably for preoperative evaluation and research.

The cortical areas involved in human speech should be characterized reliably prior to surgery for brain tumors or drug-resistant epilepsy. The functional ...

Improving Outcomes in Anteromesial Temporal Lobe Resections - A Demonstration of Resecting the Temporal Piriform Cortex

Anteromesial temporal lobe resection (ATLR) is a useful treatment option for drug-resistant mesial temporal lobe epilepsy (DRmTLE). Growing evidence suggests the piriform cortex plays a crucial role in the generation and propagation of seizures in DRmTLE - and that the resection of the temporal portion of the piriform cortex is associated with significantly improved rates of seizure freedom. 
Here, we present the resection of the temporal portion of the piriform cortex in ATLR, using high-resolution preoperative probabilistic tractography algorithms and fused anatomical masks of the structures of interest into the intraoperative neuronavigation and microscope head-up display (HUD). 
All patients undergoing comprehensive preoperative assessment and investigations for DRmTLE provided informed, written consent to record an intraoperative video of the procedure. Patients were identified by an expert multidisciplinary team of epileptologists, epilepsy neurosurgeons, neuropsychologists, neuropsychiatrists, and electrophysiologists at a large epilepsy surgery center. The preoperative imaging pipeline included the delineation of critical structures. This included the temporal piriform cortex, and high-resolution probabilistic tractography for essential tracts at risk (e.g., optic radiation and inferior fronto-occipital fasciculus). These were co-registered to the preoperative volumetric neuronavigation scan and uploaded to the intra-operative neuronavigation system. 
Presented here is a step-by-step procedure of ATLR, including the resection of the temporal portion of the piriform cortex. The protocol combines Advanced structural and diffusion MR imaging and intraoperative visual aids to integrate anatomical masks of critical grey matter structures and white matter tracts into the surgical workflow in the operating room.

Here, we demonstrate an approach to intraoperative neurosurgical guidance in anteromesial temporal lobe resections, specifically highlighting the use of tractography and anatomical masks to aid safe resection of the temporal portion of the piriform cortex - an area increasingly regarded as a crucial surgical target in drug-resistant mesial temporal lobe epilepsy.

Anteromesial temporal lobe resection (ATLR) is a useful treatment option for drug-resistant mesial temporal lobe epilepsy (DRmTLE). Growing evidence ...

Role of Diffusion MRI Tractography in Endoscopic Endonasal Skull Base Surgery

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