<strong>Optic</strong> <strong>Radiation</strong> <strong>Tractography</strong> with DTI vs. HARDItemporal lobe epilepsy without any structural changes <strong>in</strong> MRI[37]. In other cases, multi-ROI approaches were used with seedvolumes placed around the LGN and alongside the course the OR[38,44,46,51]. Furthermore, the FA-threshold for DTI-basedtractography varies significantly or is not mentioned. In somecases a threshold as low as 0.15 [45] was described, which can leadto false estimation of the created object’s volume.To obta<strong>in</strong> comparable results for DTI-, and HARDI+CS-basedfiber tractography, we used FA-thresholds of 0.18–0.2 and onlyone identical ROI around the LGN as start for the tractography.Potentials and drawbacks of HARDI+CS-based fibertractographyAs shown, we found obvious advantages of HARDI+CS-basedfiber tractography over DTI-based tractography <strong>in</strong> bra<strong>in</strong> whitematter areas of disturbed diffusion properties. This can be ofparticular neurosurgical <strong>in</strong>terest <strong>in</strong> high-grade glioma surgery ofthe temporal lobe or also for low-grade gliomas which are closelylocated to the OR, as DTI-based tractography of the OR seems tobe of m<strong>in</strong>or quality <strong>in</strong> these cases.Of course, results of fiber tractography differ for the various<strong>in</strong>tracerebral fiber bundles, so that our described f<strong>in</strong>d<strong>in</strong>gs shouldbe <strong>in</strong>vestigated and ensured for other neurosurgically relevantpathways as well, particularly for those with a neuroanatomicallycomplex course. So far, this was already done for the languageassociatedpathways <strong>in</strong> a glioma patient collective [52]. Here, wefound similar results <strong>in</strong> terms of improved tractography based onHARDI+CS, particularly <strong>in</strong> cases of closely located larger<strong>in</strong>traaxial high-grade tumors associated with <strong>in</strong>creased peritumoraledema.However, certa<strong>in</strong> drawbacks of the HARDI+CS-based fiberreconstruction have to be mentioned. Although us<strong>in</strong>g the samediffusion dataset with 30 non-coll<strong>in</strong>ear gradients, time forHARDI+CS-based fiber tractography (<strong>in</strong>clud<strong>in</strong>g the calculationof ODFs and the fiber track<strong>in</strong>g procedure itself) is significantlylonger with 45 m<strong>in</strong>utes, compared with 5 m<strong>in</strong>utes for DTI-basedtractography. In this way, cl<strong>in</strong>ical practicability is still reduced,requir<strong>in</strong>g larger effort <strong>in</strong> time and personnel. Furthermore, thesoftware platform MedAlyVis, on which HARDI+CS is implemented,is not commercially available and strongly emphazisesscientific applications. We found, that the teach-<strong>in</strong> period issignificantly longer compared with DTI-tractography applicationson cl<strong>in</strong>ically orientated and commercially used navigation systems.OutlookReferences1. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, et al. (2001) Amultivariate analysis of 416 patients with glioblastoma multiforme: prognosis,extent of resection, and survival. J Neurosurg 95: 190–198.2. McGirt MJ, Chaichana KL, Gath<strong>in</strong>ji M, Attenello FJ, Than K, et al. (2009)Independent association of extent of resection with survival <strong>in</strong> patients withmalignant bra<strong>in</strong> astrocytoma. J Neurosurg 110: 156–162.3. Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS (2011) An extentof resection threshold for newly diagnosed glioblastomas. J Neurosurg 115: 3–8.For optimization, we <strong>in</strong>tend to vary parameters (e.g. gantry tilt,voxel size, repetitions) of the diffusion imag<strong>in</strong>g sequence based forthe fiber reconstruction via DTI-, and HARDI+CS. This will firstbe <strong>in</strong>vestigated with a software phantom, provid<strong>in</strong>g a ground truthfiber bundle to objectively compare the reconstructed fibers.Subsequently, the most promis<strong>in</strong>g sequence parameters will beevaluated <strong>in</strong> a collective of healthy subjects. Furthermore,optimization of tractography data for fibers with neuroanatomicallycomplex course such the language-associated pathways, theoptic radiation or the limbic system will be <strong>in</strong>vestigated via use ofdifferent tractography algorithms applied also to the HARDI dataand compared with the tensor deflection algorithm. For future<strong>in</strong>vestigations, HARDI+CS-based reconstruction the mentionedfiber bundles should be rout<strong>in</strong>ely <strong>in</strong>tegrated <strong>in</strong>to the navigationsystem besides conventional DTI-based tractography to supportour hypothesis and evaluate the cl<strong>in</strong>ical impact on postoperativemorbidity. In this context, it should be the aim to applyHARDI+CS <strong>in</strong> an open source software platform e.g. <strong>Slicer</strong> [53].To implement the fiber object obta<strong>in</strong>ed via HARDI+CS <strong>in</strong> the<strong>in</strong>traoperatively used navigation system, a b<strong>in</strong>ary mask of thederived fiber bundle can be used for visualization. The <strong>in</strong>traoperativelydisplayed data should be compared and validated us<strong>in</strong>gthe pre-, and postoperative neurological-, and neuropsychologicalexam<strong>in</strong>ation and <strong>in</strong>traoperative electrostimulation methods, particularlysubcortical stimulation. Furthermore, <strong>in</strong> case of thelanguage-associated pathways, awake surgery can be considered <strong>in</strong>selected cases.To provide an <strong>in</strong>traoperative fiber-estimation with compensationfor bra<strong>in</strong>shift, we suggest match<strong>in</strong>g preoperatively obta<strong>in</strong>edHARDI+CS fibers with <strong>in</strong>traoperative MRI us<strong>in</strong>g non-l<strong>in</strong>earregistration or sophisticated pattern recognition techniques [54].Alternatively, non l<strong>in</strong>ear registration techniques can also beapplied to other <strong>in</strong>traoperative imag<strong>in</strong>g methods like <strong>3D</strong>ultrasound, provid<strong>in</strong>g multimodal <strong>in</strong>formation <strong>in</strong>traoperatively[55,56].ConclusionsWith our prospectively conducted case series on eight patients,we can clearly show the potential of HARDI+CS-based fibertractography compared with conventionally used DTI-based fiberreconstruction. HARDI+CS thus offers high resolution fibertractography, even for neuroanatomically complex fiber bundleslike the OR and <strong>in</strong> areas of disturbed diffusion patterns, howeverus<strong>in</strong>g low data acquisition times required for cl<strong>in</strong>ical use. In thisway, a neurosurgical major <strong>in</strong>terest focuses on glioma surgery ofthe temporal lobe, as <strong>in</strong> these cases peritumoral diffusion patternshave to be considered disturbed <strong>in</strong> any case. HARDI+CS seems tobe a promis<strong>in</strong>g approach, comb<strong>in</strong><strong>in</strong>g the advantages of HARDI’sestimation of multiple <strong>in</strong>travoxel fiber populations <strong>in</strong> the temporalstem with the cl<strong>in</strong>ical feasibility of rout<strong>in</strong>ely used DTI image dataacquisition <strong>in</strong> presurgical practice.AcknowledgmentsWe thank Joerg W. Bartsch PhD, Department of Neurosurgery, UniversityMarburg for proofread<strong>in</strong>g the manuscript.Author ContributionsConceived and designed the experiments: DK. Performed the experiments:DK MB. Analyzed the data: DK MB DM JS CN. Wrote the paper: DKMB.4. Kuhnt D, Bauer MH, Becker A, Merhof D, Zolal A, et al. (2011) Intraoperativevisualization of fiber track<strong>in</strong>g based reconstruction of language pathways <strong>in</strong>glioma surgery. Neurosurgery.5. Nimsky C, Ganslandt O, Merhof D, Sorensen AG, Fahlbusch R (2006)Intraoperative visualization of the pyramidal tract by diffusion-tensor-imag<strong>in</strong>gbasedfiber track<strong>in</strong>g. Neuroimage 30: 1219–1229.6. Basser PJ, Mattiello J, LeBihan D (1994) MR diffusion tensor spectroscopy andimag<strong>in</strong>g. Biophys J 66: 259–267.7. Basser PJ, Pajevic S, Pierpaoli C, Duda J, Aldroubi A (2000) In vivo fibertractography us<strong>in</strong>g DT-MRI data. Magn Reson Med 44: 625–632.PLOS ONE | www.plosone.org 6 July 2013 | Volume 8 | Issue 7 | e70973
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