RESEARCH—HUMAN—CLINICAL STUDIES RESEARCH—HUMAN—CLINICAL STUDIES
TOPIC
Differences Between Generalized Q-Sampling Imaging and Diffusion Tensor Imaging in the Preoperative Visualization of the Nerve Fiber Tracts Within Peritumoral Edema in Brain Hongliang Zhang, MD, PhD* Yong Wang, MD, PhD* Tao Lu, MD‡ Bo Qiu, MD, PhD* Yanqing Tang, MD, PhD§ Shaowu Ou, MD, PhD* Xinxin Tie, MD, PhD* Chuanqi Sun, MD* Ke Xu, MD, PhD‡ Yibao Wang, MD, PhD* *Department of Neurosurgery, the First Affiliated Hospital of China Medical University, Liaoning, People’s Republic of China; ‡Department of Radiology, the First Affiliated Hospital of China Medical University, Liaoning, People’s Republic of China; and §Department of Psychiatry, the First Affiliated Hospital of China Medical University, Liaoning, People’s Republic of China Correspondence: Yibao Wang, MD, PhD, Department of Neurosurgery, the First Affiliated Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, People’s Republic of China. E-mail:
[email protected]. Received, April 22, 2013. Accepted, August 23, 2013. Published Online, September 19, 2013. Copyright ª 2013 by the Congress of Neurological Surgeons
BACKGROUND: Diffusion tensor imaging (DTI) tractography enables the in vivo visualization of white matter tracts inside normal brain tissue, which provides the neurosurgeon important information to plan tumor resections. However, DTI is associated with restrictions in the resolution of crossing fibers in the vicinity of the tumor or in edema. We find that generalized q-sampling imaging (GQI) can overcome these difficulties and is advantageous over DTI for the tractography of the fiber bundle in peritumoral edema. OBJECTIVE: To demonstrate the differences between GQI and DTI in the preoperative mapping of fiber tractography in peritumoral edema of cerebral tumors, and discuss the clinical application of GQI in neurosurgical planning. METHODS: Five patients with brain tumors underwent 3-T magnetic resonance imaging scans, and the data were reconstructed by DTI and GQI. We adjusted the parameters and compared the differences between DTI and GQI in visualizing the fiber tracts in the peritumoral edema of cerebral tumors. RESULTS: GQI and DTI showed substantial differences in displaying the nerve fibers in the edema surrounding the tumor. The GQI tractography method could fully display existing intact fibers in the edema, whereas the fiber tracts in edema displayed by DTI tractography were incomplete, missing, or ruptured. CONCLUSION: GQI can visualize the tracts in the peritumoral edema of cerebral tumors better than DTI. Although GQI has many limitations, its future in the preoperative guidance of brain tumor lesions is promising. KEY WORDS: Diffusion tensor imaging, Fiber in edema, Tractography Neurosurgery 73:1044–1053, 2013
DOI: 10.1227/NEU.0000000000000146
T
he neurosurgical treatment of brain tumors aims to completely resect the pathological lesions without sacrificing the brain functions while preserving the patient’s quality of life.1 However, many brain tumors originate within the white matter of the brain, and, in most situations, the eloquent white matter tracts are displaced, ABBREVIATIONS: CST, corticospinal tract; DSI, diffusion spectrum imaging; DTI, diffusion tensor imaging; FA, fractional anisotropy; GQI, generalized q-sampling imaging; KPS, Karnofsky Performance Scale; ODF, orientation distribution function; PT, pyramidal tract; PLIC, posterior limb of internal capsule; QA, quantitative anisotropy; QBI, q-ball imaging; SDF, spin distribution function
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disrupted, or invaded by the tumor and the edema.2 Thus, distinguishing normal tissue from disrupted white matter tracts is essential before the excision of brain tumors. Conventional magnetic resonance (MR) techniques have been widely used to radiologically assess and localize brain tumors. However, these MR methods cannot yield precise 3-dimensional information about the integrity and location of white matter tracts in the region surrounding tumors.3 Diffusion tensor imaging (DTI), which is performed within a compact tract with parallel-running axonal trajectories, has presented new opportunities for analyzing the position and extent of individual fiber tracts in vivo and can preoperatively map the 3-dimensional structure of the
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brain white matter.4 However, DTI also has substantial limitations. For example, it can only resolve the single fiber direction within each voxel and cannot display crossing or branching fibers in complex regions; DTI indices will reflect the weighted average of all compartments when the partial volume of different diffusion compartments occurs and can no longer be regarded as a marker for a specific tissue. The limitation of partial volume effects is particularly true for most DT-MRI studies that use epidemiological techniques with relatively large voxels.5-8 Alexander et al9 found that the rotational partial volume effects for large voxels (1.5-5.0 mm on a side) may have led to trace variations on the order of 5% to 7% and fractional anisotropy (FA) variations on the order of 10% to 20%. Cerebrospinal fluid (CSF) contamination is a particular type of partial volume effect. Peritumoral edema in the brain, whose spread depends on the localization of the pathology that caused it, has an effect similar to that of CSF contamination.10,11 Peritumoral edema often infiltrates and contaminates brain tissues with partial volume effects. Thus, identifying the condition of the infiltrated tissue and performing tractography or other analyses is often difficult. These weaknesses limit the clinical application of DTI. Manabu Kinoshita12 presented a preliminary validation of tractography in subjects harboring brain tumors by comparing the results produced by neuronavigation and electrical white matter stimulation in 2 patients with gliomas in the eloquent area. The study found that the images failed to present the actual size of the fiber bundles, even though the fiber-tracking technique of DTI could show the pyramidal tract. In our study, some fibers that surrounded the peritumoral edema failed to show preoperatively and “reappeared” while the tumor recessed and the edema faded away. This phenomenon also demonstrated the necessity to overcome the limitations of DTI and fully validate the fibertracking technique to determine its true clinical efficacy. Several methods have been proposed to better characterize the complicated fiber patterns and discern fiber orientations. These methods can be categorized into model-based methods and modelfree methods.13 Model-based methods, which include the multiple Gaussian model, spherical harmonic decomposition, the diffusion kurtosis model, spherical harmonic deconvolution, etc, rely on a complex model to characterize the diffusion MR signals acquired by high angular resolution diffusion imaging, a scheme that samples data on a shell in the diffusion-encoding space, which is called the q-space.14 Model-free methods, also called q-space-imaging methods, are based on the Fourier transform relationship between the diffusion MR signals and the underlying diffusion displacement.15 They tackle the problem by acquiring the orientation distribution function (ODF) of the diffusion displacement. Q-ball imaging (QBI) is a type of q-space method that uses the Funk-Radon transformation to reconstruct the ODF from a high angular resolution diffusion-imaging shell data set.16 Diffusion spectrum imaging (DSI) is another q-space-imaging method,17 which acquires data using a grid-sampling scheme. A Fourier transformation was applied to the q-space data to estimate the underlying diffusion displacement pattern to then calculate the ODF. However, QBI and DSI also have limitations. The Funk-Radon
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transformation used in the QBI method only partially exploits the relationship between the MR signals and diffusion displacements; the q-ball ODF only considers the displacements perpendicular to the diffusion gradient vector instead of all the directions.18 DSI can characterize the diffusion probability density function by applying a Fourier transformation to the MR signals in the q-space, but truncation artifacts often occur during this process, and a Hanning filter is often needed to smooth the probability density function.19,20 Recently, Yeh et al21 derived a new relationship between the spin distribution function (SDF) and the MR signal. The SDF represents a quantitative distribution of the spins undergoing diffusion instead of a probability distribution of the diffusion displacement like the diffusion ODF. The SDF value unifies the scale of SDF across different voxels, so that the SDF contains a consistent physical meaning over all the voxels.21 This finding led to the application of the generalized q-sampling imaging method (GQI) to grid- or shell-sampling schemes, which can provide directional and quantitative information about the crossing fibers. We find that GQI can distinctly visualize the fiber tracts in edema around the brain tumor in clinical practice, which cannot be achieved by DTI. We performed a clinical study of 5 patients with brain tumors and heavy edema to compare the differences between GQI and DTI in the preoperative visualization of fiber tracts in peritumoral edema and discuss the clinical applications of GQI.
MATERIALS AND METHODS Patient Selection Five patients with cerebroma were enrolled in our study between July 2011 and July 2012. Five adults (1 male, 4 females; all right-handed; age range, 20-67 years of age) were patients in the ward of the First Affiliated Hospital of China Medical University. The major clinical symptoms in these patients were headache, epilepsy, and hemiparesis. All participants were diagnosed with a brain tumor by conventional MRI and scheduled for resection. The Karnofsky Performance Scale (KPS) was used to preoperatively and postoperatively to assess the degree of the patient’s functional impairment to grade the functional disturbances of daily life activities.22 The KPS score correlated positively with survival and illness severity. The final diagnosis was determined by the pathology. The internal review board, including the ethics committee at the China Medical University, approved all the procedures used here, and informed consent was obtained from all participants.
MRI Acquisition The MRI data were acquired using a 3.0T whole-body MRI scanner (General Electric Medical Systems, GE signa HDxt). Subjects were asked to lie motionlessly in the scanner. Restraining foam pads were placed on 2 sides of the head to minimize head motion, and a cotton plug was used to diminish the noise. The 3-dimensional T1-weighted images used to localize the anatomy were acquired with a brain volume imaging (BRAVO) sequence with the following imaging parameters: repetition time = 8.5 ms, echo time = 3.332 ms, inversion time = 450 ms, slice thickness = 1 mm, flip angle = 13, number of excitations = 1, field of view = 240 · 240 mm2, voxel sizes = 0.5 · 0.5 · 1.0 mm3, and acquisition time = 215 s.
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The diffusion-imaging data were acquired using a 25-direction scan single-shot spin-echo echo planar imaging sequence with a 2.4-mm slice thickness, no interslice gap, and the following specifications to fully cover the brain: repetition time = 8000 ms, echo time = 108 ms, flip angle = 90, b-values = 1000 s/m2, field of view = 240 · 240 mm2, voxel sizes = 1 · 1 · 2.4 mm3, number of excitations = 1, and 42 contiguous slices. The acquisition time was 216 s.
Diffusion Postprocessing The diffusion-imaging data were reconstructed by the DTI and GQI approach with the use of the DSI studio software (http://dsi-studio.labsolver. org/). The fibers were tracked by using the Trackvis software (http://trackvis. org/), in which the commissural tracts were depicted in red, the association fibers were displayed in green, and the super-to-inferior running projection fibers were shown in blue.
Image Processing and Analysis Because fiber tracking in diffusion-imaging tractography is a userdefined process and the results were affected by many factors, such as the size and location of seed regions of interest (ROIs), threshold of FA or quantitative anisotropy (QA),23 and the preset total fiber number of the whole brain, we set an unbiased reference in the uninjured side of the brain to convincingly visualize the fibers in the edema. First, we loaded the DICOM data of the 5 patients into DSI Studio, renamed the DICOM files, and opened DICOM files to create the “.src file.” We then opened the “.src” file to reconstruct the DTI and GQI and obtain the “.fib” data. Finally, we opened the “.fib” file to track the fibers and obtain the tractography of the DTI and GQI. We defined several parameters in the tractography interface of DTI and GQI to be the same, such as the maximum angle (50), step size (0.469), and total fiber number of the brain (10 000 or 20 000). We then marked the specific ROI and defined the FA and QA threshold. Classically, the pyramidal tract (PT) had been thought to lie in the anterior third of the posterior limb of the internal capsule (PLIC), an idea that was suggested by Charcot.24 Thus, we defined the ROI in the PLIC to use the PT in the uninjured side as the unbiased reference marker. We subsequently began to track the whole brain and isolated the PT in the uninjured side with Trackvis. We adjusted the FA threshold and QA threshold to ensure that the appearance and number of fibers in the DTI and GQI were equal. We then set the ROI of PLIC in the tumor side of the contralateral hemisphere and adjusted the ROI to capture the fibers surrounding the tumor and edema, which included PT.
Surgical Management With the assistance of the 3-dimensional imaging provided by GQI and fiber tractography, we knew the relationship between the lesion and
important fiber tracts. Most of the corticospinal tracts were posteriorly or posteriolaterally compressed. Total resections were achieved in all 5 patients. The KPS was used to evaluate the long-term quality of life for each patient (Table).
Fiber Dissection Technique We dissected the fibers at autopsy to validate their exit. One normal brain (age 61 years, male) was obtained at routine autopsy. The study was approved by the Ethics committee at China Medical University. The specimen was fixed in a 10% formalin aqueous solution for at least 4 weeks and subsequently frozen for an additional 2 weeks at 216C according to the method introduced by Ludwig and Klingler.25 The white matter tracts were progressively dissected by peeling off the gray matter and isolating the fiber bundles in their glial sheets. We dissected the fibers at the Surgical Neuroanatomy Lab of the China Medical University with the aid of microsurgical instrumentation and a surgical microscope (Carl Zeiss).
RESULTS The tractography of the fibers based on DTI and GQI methods was obtained by using the DSI Studio software, and the results for each patient were described separately. The tractography results were evaluated based on neuroanatomical knowledge. The workflows of the DTI- and GQI-based fiber tractography are described below, and the results were compared side-by-side. In general, DTI failed to delineate the fibers in the edema, but GQI displayed them well. The total numbers of PT fibers visualized by DTI were obviously less than those visualized by GQI. Case 1 was a 21-year-old male patient who presented with repeated seizures. The conventional enhanced MRI showed a spaceoccupying lesion located in the superior frontal gyrus before the central sulcus and on the left side of the falx cerebri (Figure 1A-C). The lesion was contrast-enhanced in the MR enhanced phase, and drug treatment, such as sodium valproate, could not adequately control the seizures. Thus, surgery was indicated for the patient. Because the lesion was close to the PT, we ordered diffusion MRI for the patient to visualize the shape of the PT in order to completely remove the tumor without sacrificing brain function. As described above, we adjusted the FA threshold and QA threshold in DSI Studio and found that the PTs in DTI and GQI had the same appearance when the FA threshold = 0.12 and QA threshold = 0.13, which agreed with the neuroanatomical knowledge (as demonstrated in Figure 1D and G). In both
TABLE. Patient Demographics Case 1 2 3 4 5
Sex
Age, y
Preoperative KPS
Postoperative KPS
Location
Pathology
M F F F F
21 22 67 58 20
80 70 80 70 60
100 100 90 90 100
Left frontal lobe Right frontal lobe Left temporal lobe Left parafalcine Left frontal lobe
Demyelinating pseudoneoplasm Oligodendroglioma (WHO III) Astrocytoma (WHO III) Glioblastoma (WHO IV) Atypia central neurocytoma
KPS, Karnofsky Performance Scale; WHO, World Health Organization.
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FIGURE 1. Case 1. A 21-year-old male patient experiencing repeated seizures. A, conventional MRI T2 axial plane imaging showing the space-occupying lesion located in the superior frontal gyrus with heavy edema surrounding the tumor. B and C, the enhanced MRI in the sagittal and coronal phases showed the tumor was substantially enhanced. D and G, the PTs of the uninjured side were shown by DTI and GQI with similar appearance and fiber numbers after we adjusted the FA and QA thresholds. E and H, the fibers circumscribing the tumor were visualized by DTI and GQI. F and I, the differences between DTI and GQI in displaying the fibers in edema are demonstrated by superimposing the fibers visualized by each method. Fibers visualized by GQI are shown in red, and fibers visualized by DTI are shown in blue. The white ring marked the fibers showed by GQI but failed to show in DTI. The red arrow indicated the appropriate surgical approach that could avoid injury of the fiber in edema. DTI, diffusion tensor imaging; FA, fractional anisotropy; GQI, generalized q-sampling imaging; PT, pyramidal tract; QA, quantitative anisotropy.
cases, the number of fibers was 240. We then set the ROI of PLIC at the tumor side in the contralateral hemisphere and obtained the fibers around the tumor and edema. The data demonstrated that DTI failed to delineate the fibers in the edema; the fibers in the tumor were broken off or incomplete (Figure 1E). However, GQI displayed the fibers well (Figure 1H). Superimposing the GQI and DTI results demonstrated the differences between the 2 methods in displaying the fibers in edema. The fibers visualized by GQI are shown in red, and those visualized by DTI are shown in blue (Figure 1F and I). The white ring marked the fibers showed by GQI but failed to show in DTI. The total number of fibers surrounding the tumor was 224 in DTI and 488 in GQI. As already mentioned, these numbers indicate that DTI could not
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visualize the whole intact fibers in the edema, whereas GQI could visualize them well. To clarify the internal mechanism underlying this result, we observed the FA map for fibers reconstructed by DTI and GQI (Figure 2A and B). The squares indicate the same region on the identical axial lay of the 2 FA maps, which included the tumor and edema. We magnified the region in the squares to obtain a close-up view of regions (Figure 2C and D); the red oval indicates the fibers in edema. The fibers in edema visualized by DTI showed entirely perpendicular tracking (Figure 2C). This finding contradicted the traditional fiber anatomy in the brain, which indicated that these fibers visualized by DTI were artifacts. Meanwhile, the fibers tracked in edema visualized by GQI
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FIGURE 2. Case 1. A and B, the FA maps of case 1 with fibers reconstructed by DTI and GQI. The squares indicated the same region in the identical axial layout of the 2 FA maps, which included the tumor and its posterior edema. C and D, in the close-up view of regions in the squares, the red ovals indicate the fiber regions in the edema. C, the fibers in the edema visualized by DTI showed entirely perpendicular tracking, which contradicted the traditional fiber anatomy in the brain. Thus, these fibers were artifacts. D, the fiber tracking in edema visualized by GQI showed a valid trajectory, which proved our conclusion. DTI, diffusion tensor imaging; FA, fractional anisotropy; GQI, generalized q-sampling imaging.
showed a valid trajectory (Figure 2D), which proved our conclusion. We surgically approached the anterior of the tumor (the red arrow in Figure 1H) and assessed the excision extension to avoid injuring the fibers in the edema. The patient recovered well without complications; the preoperative KPS was 80 and the postoperative KPS was 100. Case 2 was a 22-year-old woman who presented with focal seizure of the left leg without any further neurological deficits. The left leg shook severely when the seizure attacked and spontaneously stopped shaking several minutes later without residual neurological deficits. Dilantin had been used for 1 year without improvement, and the seizures continued to worsen. A right frontal solitary lesion was detected with high density in CT as well as contrast-enhanced MRI. When we adjusted the FA threshold to 0.06 and the QA threshold to 0.12, the fibers visualized by DTI and GQI had the same appearance (Figure 3A and D), and both methods indicated 199
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fibers. We then set ROI of the internal capsule at the tumor side in the contralateral hemisphere and obtained the fiber tracts around the tumor and edema. The DTI failed to delineate the tracts in the edema on the posterior of the tumor, whereas GQI could display them well (Figure 3B and E). The total number of PTs was 131 in DTI and 181 in GQI. Superimposing the DTI and GQI results clearly demonstrated the differences in displaying the fibers between the 2 methods. The fibers visualized by GQI are shown in red, and those visualized by DTI are shown blue. The white ring marked the fibers showed by GQI but failed to show in DTI. The tumor was completely removed without complications by using a transfrontal approach. This treatment completely eliminated the focal seizures of the left leg. The preoperative KPS was 70, and the postoperative KPS was 100. We reevaluated the diffusion imaging 3 months after surgery when the edema had subsided and found that fiber tracts previously undetectable by DTI “reappeared” at this time and had a similar appearance to
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FIGURE 3. Case 2. A 22-year-old woman presenting with focal seizures of the left leg. A and D, the PTs on the uninjured side as shown by DTI and GQI had similar appearances and fiber numbers after the adjustment of the FA and QA thresholds. B and E, the fibers circumscribing the tumor were shown by DTI and GQI. C and F, the differences between DTI and GQI in displaying the fibers in edema after superimpose the 2 images. Fibers visualized by GQI are shown in red, and fibers visualized by DTI are shown in blue. The white ring marked the fibers shown by GQI but failed to show in DTI. The red arrow indicates the appropriate surgical approach that could avoid injury of the fiber in the edema. G-I, the fibers displayed by DTI and GQI circumscribed the tumor resection cavity 3 months after surgery, at which point the edema had subsided. The fiber tracts that had failed to preoperatively present with DTI “reappeared” postoperatively (G) and were similar to those visualized by GQI (H) when the two were superimposed (I). This phenomenon proved that fibers present in the edema could be preoperatively displayed by GQI but not by DTI. DTI, diffusion tensor imaging; FA, fractional anisotropy; GQI, generalized q-sampling imaging; PT, pyramidal tract; QA, quantitative anisotropy.
those shown by GQI (Figure 3G-I). This phenomenon proved that fibers that were present in the preoperative edema displayed in GQI but not in DTI, which strongly supported our theory. Case 3 was a 67-year-old woman who presented with progressive aphasia caused by a lesion of the left temporal (Figure 4A). We used the arcuate fasciculus on the tumor side as the reference marker based on its important role in language. The total fibers of whole brain were preset to 20 000. When we adjusted the FA threshold to 0.07 and the QA threshold to 0.06, the arcuate fasciculus visualized by DTI and GQI had the same appearance (as demonstrated in Figure 4C and D). In both instances, the number of fibers was 175. We then set the ROI in the ipsilateral hemisphere at the edema posterior to the tumor and isolated a fiber
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bundle around the tumor and edema. We supposed that this tract, which we called the ventral language-related tract, was associated with language form and that the symptoms of progressive aphasia were related to the compression of this tract by the tumor and edema. GQI demonstrated that the tract in was intact in the edema around the tumor (Figure 4C), whereas DTI yielded an incomplete picture of this tract with caudal loss (Figure 4D). DTI showed 70 fibers, and GQI showed 83 fibers. We superimposed the fibers visualized by GQI and DTI; the fibers visualized by GQI are shown in blue, and fibers visualized by DTI are shown in red (Figure 4B). The ring indicated that the caudal side of the ventral language fiber bundle that ran cross the edema was intact in GQI images and incomplete in DTI images.
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FIGURE 4. Case 3. A 67-year-old woman presenting with progressive aphasia. A, the tumor in the temporal lobe showed a similar signal in T1, higher signal in T2, and was substantially enhanced in the enhancement phase with the edema behind the tumor. B, we adjusted the parameter with the arcuate fasciculus in the tumor side and superimposed the fibers shown by GQI and DTI. Fibers visualized by GQI are shown in blue, and fibers visualized by DTI are shown in red. The ring indicates that the caudal side of the ventral language fiber bundle that traversed the edema appeared intact in the GQI images (C) and incomplete in the DTI images (D). The red arrow indicates the appropriate surgical approach that could avoid injury of the caudal side of the edema. The exiting of the ventral language fiber was validated in the fiber dissection of the cadaver. This fiber was on the ventral side of the arcuate fasciculus (E) and connected the inferior frontal gyrus and the superior temporal gyrus (F). DTI, diffusion tensor imaging; GQI, generalized q-sampling imaging.
We dissected the fibers at autopsy to validate the exiting of the ventral language tract.26 The fiber dissection showed that the ventral language-related tract was a bundle of fibers that passed from the prefrontal region to the superior temporal gyrus via the ventral side of the arcuate fasciculus (Figure 4E and F). This finding confirmed that fiber tract truly exited and that the image of the intact fibers in the edema provided by GQI was correct. We resected the tumor from the anterior direction by using an appropriate pterional approach to avoid damaging the fibers in the edema. This approach slightly improved the postoperative aphasia. The preoperative KPS was 80, and the postoperative KPS was 90. Case 4 was a 58-year-old woman who presented with progressive headaches and hemiparesis in the right limb. Conventional enhanced MRI showed a space-occupying lesion located in
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the left parafalcine. Thus, we ordered diffusion MRI for the patient to visualize the shape of PT. Setting the FA threshold to 0.08 and QA threshold to 0.20 showed that the PTs visualized by DTI and GQI had the same appearance. In both instances, the number of fibers was 125. We then set the ROI of PLIC at the tumor side in the contralateral hemisphere and obtained the fibers around the tumor and in the edema. The result indicated that DTI failed to delineate the fibers in the edema, whereas GQI could display them well (Figure 5A and B). The total number of fibers surrounding the tumor visualized by DTI was 297 and 357 by GQI. As previously mentioned, DTI could not visualize the whole intact fibers in the edema as well as GQI could visualize them. We superimposed the fibers visualized by DTI and GQI; the fibers visualized by GQI are shown in red, and those visualized by DTI
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FIGURE 5. Case 4 and Case 5. A-D, a 58-year-old woman presenting with progressive headaches and hemiparesis of the right limb. Enhanced MRI showed a space-occupying lesion located in the left parafalcine surrounded by edema. E-H, a 20-year-old woman presenting with general seizures without further neurological deficits. A left frontal cystic solitary lesion was detected by MRI. A and B, E and F, DTI and GQI showed fibers around the tumor after we adjusted the parameters. C and D, G and H, we superimposed the fibers shown by DTI and GQI. Fibers visualized by GQI are shown in red, and fibers visualized by DTI are shown in blue. The white rings indicate that the fibers in the edema were visualized by GQI but failed to be detected by DTI. DTI, diffusion tensor imaging; GQI, generalized q-sampling imaging
are shown in blue. The white rings indicated that the fibers in the edema were visualized by GQI but were not detected by DTI. These fibers linked the cortex to the brainstem and traversed the edema at the posterior of the tumor (Figure 5C and D). We approached the tumor from the falx to avoid damaging the fibers in the edema. With the use of this approach, hemiparesis of the right limb improved after surgery. The preoperative KPS was 70, and the postoperative KPS was 90. Case 5 was a 20-year-old woman who presented with general seizures without further neurological deficits. A left frontal cystic solitary lesion was detected by MRI. We ordered diffusion MRI to visualize the shape of the PT. The ROI was set in the internal capsule. We adjusted the parameters and found that, when we set the FA threshold to 0.10 and the QA threshold to 0.25, the fibers included in the PT of DTI and GQI had the same appearance. Both instances showed 312 fibers. We then set the ROI of the internal capsule at the tumor side in the contralateral hemisphere and obtained the fiber tract around the tumor and edema. DTI failed to delineate the fibers in the edema posterior to the tumor, whereas GQI could display them well (Figure 5E and F). The total number of fibers surrounding the tumor was 273 as detected by DTI and 299 as detected by GQI. As described above, we superimposed the images obtained by the 2 methods; the fibers visualized by GQI are shown in red, and those visualized by DTI are shown in blue. The white rings indicated that the fibers in the edema could be visualized by GQI but not DTI. These fibers traversed the edema at the posterior of the tumor (Figure 5G and H). The tumor was resected by using a transfrontal approach, and we adjusted the direction and the extension of the excision to resect the tumor tissue according to the 3-dimensional imaging provided by GQI. The patient did not experience iatrogenic complications
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and was free of seizures 1 year after the operation. The preoperative KPS was 60, and the postoperative KPS was 100.
DISCUSSION Surgical resection remains the most effective treatment of neurological tumors. Cerebroma surgery aims to maximize tumor resection while avoiding injury to important adjacent tissues. Thus, the neurosurgeon must preoperatively identify the relationship between the tumor and brain structure. Many imaging technologies are used to reach this goal, such as conventional MRI, positron emission tomography, functional MRI, magnetoencephalography, etc.27 These tools are used to determine the relationship between tumors and the surrounding cortical function areas, but they provide no information concerning the shape and location of the eloquent white matter tract. Diffusion-tensor imaging (DTI) is a modified MRI technique that is sensitive to the Brownian motion of water molecules in biological tissues; it is a new clinical method that can demonstrate the integrity and orientation of white matter fibers in vivo.28 However, DTI also has some vital limitations. For example, it fails to visualize fiber tracts that are crossed, kissing, branched, or merged. In clinical practice, many neurosurgeons have also found that DTI could not adequately estimate the complex white matter structure in patients with cerebroma, especially in regions of peritumoral edema.29,30 Ng et al29 studied 12 patients who underwent resection of tumors adjacent to the corticospinal tract (CST). Even though the FA in patients whose CSTs were affected by the presence of peritumoral edema was lower than that of patients without edema, the motor control did not differ between the 2 groups. In fact, the hemiparesis was resolved in all patients, suggesting that the fiber
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tracts within the peritumoral regions were not destroyed and clinical recovery was possible. In one of the few studies with postsurgical imaging, Yamada et al30 noted the “reappearance” of the CST along with full motor recovery in a patient with right frontal glioblastoma multiforme after the resolution of the mass effect and edema. Our study agrees with their results. In case 1, the patient’s nonhemiplegia or movement difficulties contradicted with the incomplete visualization of the PT in DTI. In case 2, the fiber tracts visualized by DTI in the edema posterior to the tumor “reappeared” after the tumor was resected and the edema subsided, followed by the patient’s postoperative return to normal myodynamia. Visualizing white matter structures in regions affected by edema presents a significant challenge in the preoperative planning of surgical resections. In our study, we applied a promising new method, GQI, to visualize white matter tracts in regions of peritumoral edema. The comparison of ODFs among voxels by using QBI and DSI has thus far been impossible because each ODF is locally normalized, and the same ODF value in different voxels does not necessarily represent the same physical quantity.20 GQI, which was originally proposed by Fang-Cheng Yeh in 2010, can obtain the SDF from the shell-sampling scheme used in QBI or the grid-sampling scheme used in DSI. The SDF values are calculated by scaling the average propagator with the density function and unifying the scale of the SDF across different voxels, such that the SDF contains a consistent physical meaning over all the voxels and therefore allows intervoxel comparison.21 The simulation results confirm the accuracy of the GQI method, and the in vivo images and tractography generated from GQI are similar to those generated from QBI and DSI. Thus, the GQI method can provide directional and quantitative information about the crossing fibers and fiber tracts in complex white matter tissue. In this study, we confirm the ability of GQI to overcome the limitations of DTI in visualizing the fibers in the edema of cerebroma. In case 1, the patient exhibited good preoperative body movement, which indicated that the PT around the tumor remained intact. However, the fibers of the PT in the edema appeared incomplete in the DTI but intact in the GQI images, which proved the accuracy of GQI. To validate the exiting of ventral language-related tract in case 3, we resected the fibers at autopsy. Our findings confirmed the exiting of the fiber tract and the accuracy of GQI in displaying the intact fiber in the edema. We determined the appropriate surgical approach with 3-dimensional tractography imaging demonstrated by GQI and ultimately maximized the tumor resection while avoiding injury to important adjacent tissues. Therefore, we conclude that GQI can visualize the tracts in the peritumoral edema of cerebral tumors better than DTI, and, thus, GQI presents a promising technique for the future preoperative examination of brain tumor lesions. Limitations Even though GQI can better quantify and visualize fiber tracts in tumor-related regions like edema, it still has several noteworthy
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limitations. These limitations exist in nearly all diffusion MRI methods and have been disputed for several years. First, diffusion MRI fiber tracking is a user-defined process. The tracking results are a function of the FA threshold, angular threshold, step length, and number of samples in a voxel length.31 Choosing different parameters can result in different fiber tracts, so the practical applicability of diffusion-imaging methods remains disputed. Second, the tracked volumes also depend on the sizes and locations of the seed ROIs. Different ROIs can result in completely different fiber tracts, which complicates the isolation of tracts of interest.18 This method can also suffer from artifacts. Third, brain shift limits the accuracy of diffusion MR-imaged fiber tracks when preoperative data are transferred to the image guidance neuronavigation system.32 The goals of this study were limited by the sample size and tumor types. The signal parameters of white matter involvement with a tumor can be arranged into various categories with diffusion imaging: tract displacement (normal signal with altered position or direction), vasogenic edema (decreased signal with normal direction and location), and tumor infiltration (decreased signal with disrupted maps, fiber tract destruction, and loss of anisotropic signal).33 Further studies will require a larger sample size to confirm the ability of GQI to visualize the fiber tracts in all types of pathological tissues.
CONCLUSION Despite these limitations, GQI provides a new way to preoperatively visualize the fiber tracts in edema. This method constitutes an improvement over DTI. The advantages of functional MRI, navigation, intraoperative cortical, and subcortical electrical stimulation can be incorporated with GQI, which may further demonstrate the validity of GQI and broaden its applications until it is ultimately accepted as a conventional neurosurgical planning tool. Disclosures This study was supported by grants the from National Natural Science Foundation of China (No.81070965 and No. 30700249 to Dr Wang), Chinese National Natural Science Foundation of Youth Science Foundation (No. 81000565 to Dr Wang), Liaoning Provincial Natural Science Foundation of China (No. 2013021075 to Dr Qiu), National Natural Science Foundation of China (No. 81071099 to Dr Tang) and Science and Technology Program of Shenyang City (No. F12-277-1-04 to Dr Ou). The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
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TRACTOGRAPHY IN PERITUMORAL EDEMA
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COMMENT
D
espite of its fundamental limitations, diffusion tensor imaging (DTI)-based tractography is still the most widely applied tractography method in neurosurgical settings to delineate major white matter tracts. Correct identification of areas of fiber crossings is not possible by standard DTI because of its inability to resolve more than a single axon direction within each imaging voxel. Techniques that can resolve multiple axon directions within a single voxel may solve the problem of white matter fiber crossings, as well as the problem to reconstruct the correct white matter insertions into the cortex. Further challenges in the clinical setting relate to the effects of edema surrounding a tumor where fiber tracking is performed. Effects of the edema and the tumor itself impede the correct tracking so that either existing fibers are not visualized at all or even an erroneous tracking may result. The authors implemented a technique called generalized q-sampling imaging (GQI) with which they could demonstrate in a series of 5 patients that their technique provided results in the vicinity of a tumor that seemed to be more reliable than those obtained by DTI-based tractography. There are various technical attempts to approach the limitations of DTI-based tractography; an agreed standard or ideal solution has not yet been defined. It will be important to compare the different approaches especially with respect to their reliability and also clinical applicability. At the moment however, most neurosurgeons use the DTI-tractography method, because it is easily available, eg, as a software package in navigation systems. It is mandatory that either these commercial systems become more open to facilitate integration of better solutions or the technical advantages should be directly implemented in the commercial systems, so that they can be available for the whole neurosurgical community. Christopher Nimsky Marburg, Germany
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