Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Integration of BOLD-fMRI and DTI into radiation treatment planning for high-grade gliomas located near the primary motor cortexes and corticospinal tracts

Integration of BOLD-fMRI and DTI into radiation treatment planning for high-grade gliomas located... Background: The main objective of this study was to evaluate the efficacy of integrating the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) data into radiation treatment planning for high-grade gliomas located near the primary motor cortexes (PMCs) and corticospinal tracts (CSTs). Methods: A total of 20 patients with high-grade gliomas adjacent to PMCs and CSTs between 2012 and 2014 were recruited. The bilateral PMCs and CSTs were located in the normal regions without any overlapping with target volume of the lesions. BOLD-fMRI, DTI and conventional MRI were performed on patients (Karnofsky performance score ≥ 70) before radical radiotherapy treatment. Four different imaging studies were conducted in each patient: a planning computed tomography (CT), an anatomical MRI, a DTI and a BOLD-fMRI. For each case, three treatment plans (3DCRT, IMRT and IMRT_PMC&CST) were developed by 3 different physicists using the Pinnacle planning system. Results: Our study has shown that there was no significant difference between the 3DCRT and IMRT plans in terms of dose homogeneity, but IMRT displayed better planning target volume (PTV) dose conformity. In addition, we have found that the Dmax and Dmean to the ipsilateral and contralateral PMC and CST regions were considerably decreased in IMRT_PMC&CST group (p <0.001). Conclusions: In conclusion, integration of BOLD-fMRI and DTI into radiation treatment planning is feasible and beneficial. With the assistance of the above-described techniques, the bilateral PMCs and CSTs adjacent to the target volume could be clearly marked as OARs and spared during treatment. Keywords: High-grade gliomas, Blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI), Diffusion tensor imaging (DTI), Three-dimensional conformal radiation treatment (3DCRT), Intensity-modulated radiation therapy (IMRT), Radiation treatment planning Background conformal radiotherapy (3DCRT) has been considered as Gliomas, which contain oligodendroglia, astrocytic and the standard therapy for patients with high-grade gliomas ependymal lesions are the most common primary intracra- and intensity-modulated radiotherapy (IMRT) is becoming nial tumors. High-grade gliomas, which make up 35 to 45% increasingly used to improve dose conformity and spare of all newly diagnosed primary brain tumors worldwide, critical normal tissues. However, the risk of radiation- have a very poor prognosis [1]. The three-dimensional induced brain injury increases with the increase of radi- ation dose [2-4]. The strenuous endeavor has been made to * Correspondence: [email protected] diminish radiation complications. Equal contributors With the assistance of conventional magnetic resonance Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China imaging (MRI) and planning computed tomography (CT) Ningxia Key Laboratory for Cerebrocranial Diseases, Yinchuan, China data, many critical intracranial structures, such as lens, Full list of author information is available at the end of the article © 2015 Wang et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. Radiation Oncology (2015) 10:64 Page 2 of 7 optic nerves and optic chiasm are well demarcated. How- 240 mm × 240 mm ,flipangle=90°,NEX=1,3mm thick- ever, it is difficult to accurately locate eloquent cortices ness). A block design paradigm (5 cycles, 30 sec on and and fiber connections in the white matter of the brain by 30 sec off) was utilized. Functional areas relevant to each routine neuroimaging. Excessive irradiation of eloquent treatment region were probed by Somatosensory tasks cortices and white matter fiber tracts is unavoidable. Blood (finger tapping with audio cue). Following the acquisition of oxygen level dependent functional magnetic resonance the functional data, gadolinium-enhanced high-resolution imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) images were acquired (TR/TE = 450/14, flip angle = 90°, have recently been used to identify the primary motor cor- matrix = 256 × 256, FOV = 240 mm × 240 mm ,and slice texes (PMCs) and corticospinal tracts (CSTs). These im- thickness 3 mm skip 0 mm). After the images were taken, aging techniques have been implemented in modern data were transferred to the Matlab workstation for analysis. neuronavigation systems and used to guide the surgical re- The DTI data acquisition sequence was a spin echo-echo moval of critically located intracranial lesions [5,6]. The planar imaging (SE-EPI) sequence with TR = 10,000 ms, purpose of our study was to evaluate whether the incorp- TE = 98.8 ms, acquisition matrix = 128 × 128 pixels; FOV = oration of BOLD-fMRI and DTI data into the 3D treat- 240 mm × 240 mm ; slice thickness = 3.0 mm. Diffusion- ment planning process could spare the healthy brain and weighted imaging with b factor of 1,000 mm /s was taken sensitive parts of the brain from high doses of radiation. along 25 noncollinear directions. The acquisition time of DTI sequence was 280 seconds. DTI data was analyzed on- Methods line by the advantage workstation of the MR scanner (AW Ethical Approval was obtained from the General Hospital 4.4). For CST analysis, a seed region of interest (ROI) and a of Ningxia Medical University Review Board and written target ROI were placed on the posterior limb of the internal informed consent was obtained from patients. The study capsule and pons (anterior blue portion on the color map). was conducted with strict adherence to the Declaration of Fiber tracking employed fractional anisotropy (FA) threshold Helsinki Principles. of 0.2 and a tract angular change of 30°. The color-coded FA maps were merged with the anatomical MRI images. Re- Subjects gions of interest were drawn on the fused FA maps. A total of 20 patients with high-grade gliomas adjacent The fused fMRI activation maps and the white matter to PMCs and CSTs between May 2012 and February tracts overlaid on the anatomical MRI volume were 2014 were recruited from the General Hospital of exported as separate grayscale dicom images and loaded Ningxia Medical University, China. Eleven male patients onto Pinnacle planning system software version 9.2 (Phi- and 9 female patients aged from 24 to 66 year-old were lips Medical Systems, Netherlands). The anatomical MRI enrolled in this study. images were registered with the CT volume for each pa- The glioma tissues in our study included 14 astrocyto- tient. Figure 1 shows the anatomical MRI images were mas (WHO Grade III) and 6 glioblastomas (WHO Grade IV). The bilateral PMCs and CSTs were located in the nor- mal regions without any overlapping with target volume of the lesions. BOLD-fMRI, DTI and conventional MRI were performed on patients (Karnofsky performance score ≥ 70) before radical radiotherapy treatment. Data acquisition and analysis Four different imaging studies were conducted in each patient: a planning CT for radiosurgery treatment and target tracking during radiation therapy treatment deliv- ering; an anatomical MRI to deliver a complete set of morphological MR data; a DTI to provide white matter tractography and a BOLD- fMRI to provide brain activa- tion maps. Axial CT images (3-mm slice thickness) were taken by a wide-bore Siemens Somatom Sensation Open CT scanner (Siemens, Germany). MRI volumes were ac- quired using a Signal HDx 3.0 T MRI scanner (General Electric Company, USA). BOLD fMRI data were obtained using fat-saturated Figure 1 T1-weighted MR imaging and the corresponding axial single-shotgradientechoplanarimaging (EPI) (TE=35ms, CT after registration. TR = 3,000 ms, acquisition matrix = 64 × 64 pixels, FOV = Wang et al. Radiation Oncology (2015) 10:64 Page 3 of 7 registered with the corresponding axial CT planes for a (GTV) was described as the operative cavity with any glioma case. remaining contrast-enhancing tissue on T1-weighted mag- netic resonance imaging or as unresected enhancing tumor. Treatment planning The initial clinical target volume (CTV1) was defined as the The target and organs at risk (OARs), i.e., optic nerves, T2 hyper intensity area (edema) with a 20 mm expansion. optic chiasm and brain stem were precisely described using An initial planning target volume (PTV1) was created by CT/anatomical MRI images. Both eyes were protected to adding a 30 mm expansion to the CTV1 to account for avoid beam damage during treatment planning. The PMCs setup uncertainties. A second clinical target volume (CTV2) and the CSTs situated near the target were defined by a was defined as the contrast enhancement region in T1 with radiologist and a neurosurgeon, using the tractography im- an additional 25 mm margin. A PTV2 was generated by ages and the fused activation maps. Gross tumor volume adding a 30 mm expansion to the CTV2. Figure 2 Axial isodose distribution in a patient with high-grade glioma. The A, B and C show the dose distributions for 3DCRT, IMRT and IMRT_ PMC&CST, respectively. (orange) ipsilateral PMC (red square symbol) contralateral PMC (pink square symbol) ipsilateral CST (green square symbol) contralateral CST. Wang et al. Radiation Oncology (2015) 10:64 Page 4 of 7 Table 1 Comparison of target volume coverage between For each case, three treatment plans were developed by 3DCRT and IMRT 3 different physicists using the Pinnacle planning system. 3DCRT IMRT tp The first physicist created conventional 3DCRT plans (3DCRT) and the PMCs and the CSTs situated near the PTV1 (50 Gy) target were not taken in account by the physicist. The tar- D (Gy) 65.06 ± 0.46 64.88 ± 0.66 1.461 0.160 max get and standard morphological OARs were considered in D (Gy) 59.78 ± 0.77 59.91 ± 0.85 −0.551 0.588 mean this plan. The second physicist developed IMRT plans CI 1.219 ± 0.054 1.071 ± 0.025 10.492 <0.001* (IMRT) and the PMCs and the CSTs situated near the tar- HI 0.210 ± 0.008 0.213 ± 0.012 −1.177 0.254 get were not considered by the physicist. The third physi- PTV2 (60 Gy) cist developed IMRT plans (IMRT_PMC&CST), and the PMCs and the CSTs situated near the target were consid- D (Gy) 65.06 ± 0.46 64.88 ± 0.66 1.461 0.160 max ered. Figure 2 shows the axial isodose distribution of a pa- D (Gy) 62.46 ± 0.39 62.36 ± 0.53 1.301 0.209 mean tient with high-grade glioma. CI 1.178 ± 0.082 1.055 ± 0.049 5.552 <0.001* The treatment plans met the requirement that at least HI 0.086 ± 0.022 0.082 ± 0.016 0.809 0.429 95% of the PTV receives the prescribed dose. Cumula- *Significant difference. tive doses to the lenses, optic nerves, optic chiasm, and brainstem were limited to a maximum dose of 54 Gy for the last three structures and as low as practically achiev- homogeneity, but IMRT displayed better PTV dose con- able for the former. For conventional 3DCRT treatment, formity. Regarding the comparison of PTV1 Dmax, the prescribed dose was 50 Gy to the PTV1, immediately PTV1 Dmean, PTV2 Dmax and PTV2 Dmean, there followed by 10 Gy to the PTV2, with a total cumulative was no significant difference between the 3DCRT and dose of 50 Gy to the PTV1 and 60 Gy to the PTV 2 both IMRT plans. The dosimetric details of brainstem, optic at 2 Gy per fraction. For IMRT plans, the prescribed chiasm, optic nerves, and lenses revealed no significant dose was 50 Gy to the PTV1 and 60 Gy to the PTV2, differences between the two plans and all of these organs which were delivered concurrently over 30 daily frac- were strictly maintained within the dose limitations. The tions, with a fractional dose of 2 Gy to the PTV2. Dmax and Dmean of PMCs and CSTs were observed in both 3DCRT and IMRT plans (Table 3); however no sig- Comparison criteria for the radiation treatment plans nificant difference was found between the two plans. The dose volume histograms (DVH) data were obtained from each patient. The dose coverage was analyzed accord- Comparison of target volume coverage and OAR sparing ing to the mean dose (Dmean), maximum dose (Dmax), con- between IMRT and IMRT_PMC&CST formity index (CI) and homogeneity index (HI). The CI was Treatment plan parameters are shown in Tables 4 and 5. defined as follows [7]: CI = VRI/PTV, where VRI represents According to the data presented, both PTV1 and PTV2 the volume covered by the prescription dose. A CI value of 1.0 indicates that the volume of the prescription isodose sur- face is equal to that of the PTV. The HI was defined as fol- Table 2 Comparison of OAR sparing between 3DCRT and lows [8]: HI = (D2 − D98)/D50, where Dx% represents the IMRT dose delivered to x% of the PTV. Lower HI values indicate a 3DCRT (Gy) IMRT (Gy) tp more homogeneous target dose. OARs (e.g., brainstem, optic Ipsilateral lens D 1.99 ± 1.00 2.67 ± 1.67 −1.938 0.068 max chiasm, optic nerves, and lenses) and PMCs and CSTs were Ipsilateral lens D 1.52 ± 0.75 1.98 ± 1.45 −1.454 0.162 mean compared based on the values of Dmax and Dmean. Contralateral lens D 1.71 ± 0.74 2.38 ± 1.97 −1.885 0.075 max Contralateral lens D 1.34 ± 0.55 1.84 ± 1.69 −1.585 0.129 mean Statistical analyses Ipsilateral optic nerve D 12.54 ± 17.85 12.32 ± 13.38 0.156 0.877 The comparison of parameters between different plans was max analyzed by the paired two-tailed Student t test. Differences Ipsilateral optic nerve D 8.55 ± 11.99 8.57 ± 9.40 −0.014 0.989 mean were considered statistically significant at p < 0.05. Contralateral optic 7.55 ± 8.94 7.02 ± 7.68 1.025 0.318 nerve D max Results Contralateral optic 5.14 ± 5.92 4.59 ± 4.76 1.364 0.188 nerve D Comparison of target volume coverage and OAR sparing mean between 3DCRT and IMRT Optic chiasm D 12.53 ± 15.50 12.76 ± 13.53 −0.241 0.812 max Parameters related to dose coverage planning for Optic chiasm D 9.22 ± 11.64 8.28 ± 8.70 1.060 0.302 mean 3DCRT and IMRT are presented in Tables 1 and 2. The Brainstem D 14.78 ± 14.77 14.04 ± 11.62 0.523 0.607 max results indicated that there was no significant difference Brainstem D 7.09 ± 8.31 6.52 ± 6.99 0.711 0.486 mean between the 3DCRT and IMRT plans in terms of dose Wang et al. Radiation Oncology (2015) 10:64 Page 5 of 7 Table 3 Comparion of radiation dose between 3DCRT and Table 5 Comparison of OAR sparing between IMRT and IMRT IMRT_PMC&CST 3DCRT (Gy) IMRT (Gy) tp IMRT (Gy) IMRT_PMC&CSTtp (Gy) Ipsilateral PMC D 46.50 ± 8.65 46.54 ± 7.77 −0.050 0.960 max Ipsilateral lens D 2.67 ± 1.67 2.76 ± 1.64 −1.574 0.132 max Ipsilateral PMC D 28.45 ± 7.78 27.67 ± 8.06 1.429 0.169 mean Ipsilateral lens D 1.98 ± 1.45 2.03 ± 1.50 −1.294 0.211 mean Contralateral PMC D 24.86 ± 9.89 21.40 ± 10.94 1.542 0.140 max Contralateral lens D 2.38 ± 1.97 2.43 ± 1.95 −1.063 0.126 max Contralateral PMC D 14.73 ± 6.02 14.11 ± 7.57 0.390 0.701 mean Contralateral lens 1.84 ± 1.69 1.89 ± 1.72 −0.940 0.359 Ipsilateral CST D 51.26 ± 4.24 50.61 ± 4.72 1.801 0.088 max mean Ipsilateral CST D 36.51 ± 6.63 36.06 ± 7.57 0.893 0.383 mean Ipsilateral optic nerve 12.32 ± 13.38 12.44 ± 13.91 −0.599 0.556 Contralateral CST D 35.64 ± 10.15 36.11 ± 10.05 −0.859 0.401 max max Ipsilateral optic nerve 8.57 ± 9.40 8.78 ± 10.08 −1.126 0.274 Contralateral CST D 20.97 ± 7.43 18.90 ± 7.45 1.454 0.162 mean mean Contralateral optic 7.02 ± 7.68 7.07 ± 7.71 −0.353 0.728 nerve D max (Dmax, Dmean, CI and HI) were analyzed and showed no significant differences between two groups. The Dmax Contralateral optic 4.59 ± 4.76 4.66 ± 4.95 −0.729 0.475 nerve D mean and Dmean to these conventional OARs (e.g., brainstem, Optic chiasm D 12.76 ± 13.53 12.49 ± 13.20 1.488 0.153 optic chiasm, optic nerves, and lenses) showed no signifi- max cant differences between the two plans. The Dmax to the Optic chiasm D 8.28 ± 8.70 8.20 ± 8.63 0.573 0.573 mean ipsilateral and contralateral PMC and CST regions was Brainstem D 14.04 ± 11.62 13.56 ± 11.08 1.260 0.223 max considerably decreased by 28.7%, 24.5%, 20.2% and 37.6%, Brainstem D 6.52 ± 6.99 6.46 ± 7.05 0.790 0.439 mean respectively. The Dmean to the ipsilateral and contralat- eral PMC and CST regions was considerably decreased by 27.8%, 30.4%, 23.1% and 33.4%, respectively (Table 6). The DTI and BOLD-fMRI have recently been used to identify the white-matter pathways and functional struc- tures of the brain. In our previous study, we proposed a Discussion clinically feasible protocol of integrating BOLD-fMRI Radiation therapy is commonly applied to the brain tu- and DTI to optimize the extent of resection involving mors due to its ability to control cell growth; however, the cortical motor areas and subcortical white matter radiation therapy can have detrimental effects on the tracts in patients with brain gliomas. Those information central nervous system causing neurological complica- helped neurosurgeons resected the maximum amount of tions. The response of cerebral tissue to radiation can tumor while still preserving the most critical cortices of lead to the deficits in neural functions [9,10]. The extent the brain, thus resulting in enhanced postoperative quality of neurologic deficit is associated with the location and of life for patients [13]. The incorporation of this informa- size of radiation-induced brain injury [11,12]. Efforts tion for radiosurgery planning has also been suggested. dedicated to the precise division of brain lesions have Liu et al. has reported a novel method to integrate the been made to reduce the risk of neurological complica- fMRI brain activation map with treatment planning for tions caused by the radiation therapy. stereotactic radiosurgery (SRS). Direct irradiation of the eloquent cortices was avoided by multiple radiation arcs Table 4 Comparison of target coverage between IMRT or static radiation beams in SRS planning, and the average and IMRT_PMC&CST Table 6 Comparion of radiation doses betweeen IMRT IMRT IMRT_PMC&CST tp and IMRT_PMC&CST PTV1 (50 Gy) IMRT (Gy) IMRT_PMC& tp D (Gy) 64.88 ± 0.66 65.04 ± 0.70 −0.806 0.430 CST (Gy) max D (Gy) 59.91 ± 0.85 59.85 ± 0.68 0.633 0.534 Ipsilateral PMC D 46.54 ± 7.77 33.20 ± 11.13 7.304 <0.001 mean max CI 1.071 ± 0.025 1.073 ± 0.024 −1.077 0.295 Ipsilateral PMC D 27.67 ± 8.06 19.99 ± 8.78 7.150 <0.001 mean HI 0.213 ± 0.012 0.209 ± 0.016 0.911 0.374 Contralateral PMC D 21.40 ± 10.94 16.16 ± 9.07 5.250 <0.001 max PTV2 (60 Gy) Contralateral PMC D 14.11 ± 7.57 9.82 ± 5.62 5.276 <0.001 mean D (Gy) 64.88 ± 0.66 65.04 ± 0.70 −0.806 0.430 Ipsilateral CST D 50.61 ± 4.72 40.37 ± 6.55 9.233 <0.001 max max D (Gy) 62.36 ± 0.53 62.41 ± 0.56 −0.287 0.777 Ipsilateral CST D 36.06 ± 7.57 27.72 ± 8.87 8.032 <0.001 mean mean CI 1.055 ± 0.049 1.039 ± 0.047 1.643 0.117 Contralateral CST D 36.11 ± 10.05 22.52 ± 10.36 6.959 <0.001 max HI 0.082 ± 0.016 0.089 ± 0.016 −1.646 0.116 Contralateral CST D 18.90 ± 7.45 12.59 ± 5.51 6.362 <0.001 mean Wang et al. Radiation Oncology (2015) 10:64 Page 6 of 7 dose reduction to the eloquent cortices was 32% [14]. In Abbreviations BOLD-fMRI: Blood oxygen level dependent functional magnetic resonance addition, it has been reported that the risk of radiation- imaging; DTI: Diffusion tensor imaging; 3DCRT: Three-dimensional conformal induced neuropathy was minimized by the integration of radiation treatment; PMCs: Primary motor cortexes; CSTs: Corticospinal tracts; tractography of the brain white matter with DTI into radi- CT: Computed tomography; OARs: Organs at risk; IMRT: Intensity-modulated radiation therapy; IMRT_ PMC&CST: Intensity-modulated radiotherapy ation treatment planning of radiosurgery using Gamma planning with PMC and CST information; WHO: World Health Organization; Knife [15]. Moreover, Pantelis et al. has demonstrated that MRI: Magnetic resonance imaging; SE-EPI: Spin echo-echo planar imaging; critical structures of brain could be marked and spared ROI: Region of interest; GTV: Gross tumor volume; CTV1: Initial clinical target volume; PTV1: Initial planning target volume; CTV2: Second clinical target with the aid of the integration of BOLD-fMRI and DTI volume; PTV2: Second planning target volume; DVHs: Dose volume into CyberKnife stereotactic radiosurgery [16]. histograms; Dmax: The maximum dose; Dmean: Mean dose; CI: Conformity In this study, BOLD-fMRI and DTI were used to localize index; HI: Homogeneity index. the bilateral PMCs and CSTs and the information obtained Competing interests from these two technologies were integrated into radiation The authors declare that they have no competing interests. treatmentplanning.The firstpartofour study (3DCRT versus IMRT) indicated that there was no significant Authors’ contributions XDW, HCX, XYH and XXJ conceived the study and draft the manuscript. reduction in the dose to bilateral PMCs and CSTs between MLW and XDW performed the statistical analysis and drafted the manuscript. the 3DCRT and IMRT plans. The critical structures adja- HM, YHG, XSX, YLG and HH participated in the analysis of the treatment of cent to the target volume marked as OARs can be better radiotherapy plans and draft this manuscript. YX edited this manuscript. All authors read and approved the final manuscript. spared during the IMRT planning process due to a steep dose gradient and a high conformity [17,18]. The second Acknowledgements part of our study (IMRT versus IMRT_ PMC&CST), has This work was supported by the Natural Science Foundation of China (Grant No. 81260373) and the Natural Science Foundation of Ningxia shown that a significant reduction in the dose to bilateral (Grant No. NZ11269). PMCs and CSTs regions can be achieved without com- promising the coverage of planning target volume and the Author details Department of Radiology, General Hospital of Ningxia Medical University, limiting dose to these conventional OARs. Yinchuan, China. Ningxia Key Laboratory for Cerebrocranial Diseases, Sparing of the bilateral PMCs and CSTs does not repre- Yinchuan, China. Department of Neurosurgery, General Hospital of Ningxia sent any significant breakthrough in the treatment of brain Medical University, Yinchuan, China. Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, China. Department tumors, but we have demonstrated that it is feasible to re- of Radiology, Xi’an NO.1 Hospital, Xi’an, China. Tissue Organ Bank & Tissue duce the irradiation of critical structures adjacent to the Engineering Centre, General Hospital of Ningxia Medical University, Yinchuan, target volume. The development of the most appropriate Ningxia, China. Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin IMRT plan for the patient could be achieved by the identi- Grove, QLD, Australia. fication of the important functional structures of the brain tissues proximal to the tumors. Sparing these vital func- Received: 28 October 2014 Accepted: 19 February 2015 tional structures is important to maintain quality of life, even in those patients with restricted life expectancy. The References current study has shown that the DTI examination and 1. Chang J, Narayana A. Functional MRI for radiotherapy of gliomas. Technol MR Spectroscopy are valuable tools to differentiate the Cancer Res Treat. 2010;9(4):347–58. 2. Bleehen NM, Stenning SP. A Medical Research Council trial of two postoperative recurrent glioma from the radiation injury radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The for patients with a glioma [19,20]. Medical Research Council Brain Tumour Working Party. Br J Cancer. We are currently investigating paradigms for Broca’s 1991;64(4):769–74. 3. Butler JM, Rapp SR, Shaw EG. Managing the cognitive effects of brain tumor and Wernicke’s areas (speech center), Broadmann-17 radiation therapy. Curr Treat Options Oncol. 2006;7(6):517–23. functional structures (visual center) and optic tracts. 4. Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: The application of the fMRI in low grade cases has also current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995;31(4):983–98. been validated. 5. Kamada K, Todo T, Masutani Y, Aoki S, Ino K, Takano T, et al. Combined use of tractography-integrated functional neuronavigation and direct fiber Conclusions simulation. J Neurosurg. 2005;102(4):664–72. 6. Pirotte B, Voordecker P, Neuroschl C, Baleriaux D, Wikler D, Metens T, et al. In conclusion, integration of BOLD-fMRI and DTI into Combination of functional magnetic resonance imaging-guided radiation treatment planning is feasible and beneficial. neuronavigation and intraoperative cortical brain mapping improves With the assistance of the above-described techniques, the targeting of motor cortex stimulation in neuropathic pain. Neurosurgery. 2008;62(6 Suppl 3):941–56. structures adjacent to suspicious cancerous lesions could 7. Feuvret L, Noël G, Mazeron JJ, Bey P. Conformity index: a review. Int J Radiat be clearly marked as OARs and spared during treatment. Oncol Biol Phys. 2006;64(2):333–42. However, a wider investigation and the longer-term 8. Hodapp N. The ICRU report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT). Strahlenther clinical follow up are required to further validate the Onkol. 2012;188(1):97–9. effect of the integration of BOLD-fMRI and DTI on spar- 9. Keime-Guibert F, Napolitano M, Delattre JY. Neurological complications of ingnormaltissues. radiotherapy and chemotherapy. J Neurol. 1998;245(11):695–708. Wang et al. Radiation Oncology (2015) 10:64 Page 7 of 7 10. DeAngelis LM, Delattre J-Y, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989;39(6):789–96. 11. Flickinger JC, Kondziolka D, Lunsford LD, Kassam A, Phuong LK, Liscak R, et al. Development of a model to predict permanent symptomatic postradiosurgery. Int J Radiat Oncol Biol Phys. 2000;46(5):1143–8. 12. Voges J, Treuer H, Sturm V, Büchner C, Lehrke R, Kocher M, et al. Risk analysis of linear accelerator radiosurgery. Int J Radiat Oncol Biol Phys. 1996;36(5):1055–63. 13. Jia XX, Yu Y, Wang XD, Ma H, Zhang QH, Huang XY, et al. fMRI-driven DTT assessment of corticospinal tracts prior to cortex resection. Can J Neurol Sci. 2013;40(4):558–63. 14. Liu WC, Schulder M, Narra V, Kalnin AJ, Cathcart C, Jacobs A, et al. Functional magnetic resonance imaging aided radiation treatment planning. Med Phys. 2000;27(7):1563–72. 15. Maruyama K, Kamada K, Shin M, Itoh D, Aoki S, Masutani Y, et al. Integration of threedimensional corticospinal tractography into treatment planning for gamma knife surgery. J Neurosurg. 2005;102(4):673–7. 16. Pantelis E, Papadakis N, Verigos K, Stathochristopoulou I, Antypas C, Lekas L, et al. Integration of functional MRI, white matter tractography in stereotactic radiosurgery clinical practice. Int J Radiat Oncol Biol Phys. 2010;78(1):257–67. 17. Moretto F, Rampino M, Munoz F, Ruo Redda MG, Reali A, Balcet V, et al. Conventional 2D (2DRT) and 3D conformal radiotherapy (3DCRT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer treatment. Radiol Med. 2014;119(8):634–41. 18. Arbea L, Ramos LI, Martinez-Monge R, Moreno M, Aristu J. Intensity- modulated radiation therapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC): dosimetric comparison and clinical implications. Radiat Oncol. 2010;5:17. 19. Xu JL, Li YL, Lian JM, Dou SW, Yan FS, Wu H, et al. Distinction between postoperative recurrent glioma and radiation injury using MR diffusion tensor imaging. Neuroradiology. 2010;52(12):1193–9. 20. Rabinov JD, Lee PL, Barker FG, Louis DN, Harsh GR, Cosgrove GR, et al. In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience. Radiology. 2002;225(3):871–9. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Integration of BOLD-fMRI and DTI into radiation treatment planning for high-grade gliomas located near the primary motor cortexes and corticospinal tracts

Download PDF
7 pages

Loading next page...
 
/lp/springer-journals/integration-of-bold-fmri-and-dti-into-radiation-treatment-planning-for-fSg4dIRGWV

References (21)

Publisher
Springer Journals
Copyright
2015 Wang et al.; licensee BioMed Central.
eISSN
1748-717X
DOI
10.1186/s13014-015-0364-1
Publisher site
See Article on Publisher Site

Abstract

Background: The main objective of this study was to evaluate the efficacy of integrating the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) data into radiation treatment planning for high-grade gliomas located near the primary motor cortexes (PMCs) and corticospinal tracts (CSTs). Methods: A total of 20 patients with high-grade gliomas adjacent to PMCs and CSTs between 2012 and 2014 were recruited. The bilateral PMCs and CSTs were located in the normal regions without any overlapping with target volume of the lesions. BOLD-fMRI, DTI and conventional MRI were performed on patients (Karnofsky performance score ≥ 70) before radical radiotherapy treatment. Four different imaging studies were conducted in each patient: a planning computed tomography (CT), an anatomical MRI, a DTI and a BOLD-fMRI. For each case, three treatment plans (3DCRT, IMRT and IMRT_PMC&CST) were developed by 3 different physicists using the Pinnacle planning system. Results: Our study has shown that there was no significant difference between the 3DCRT and IMRT plans in terms of dose homogeneity, but IMRT displayed better planning target volume (PTV) dose conformity. In addition, we have found that the Dmax and Dmean to the ipsilateral and contralateral PMC and CST regions were considerably decreased in IMRT_PMC&CST group (p <0.001). Conclusions: In conclusion, integration of BOLD-fMRI and DTI into radiation treatment planning is feasible and beneficial. With the assistance of the above-described techniques, the bilateral PMCs and CSTs adjacent to the target volume could be clearly marked as OARs and spared during treatment. Keywords: High-grade gliomas, Blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI), Diffusion tensor imaging (DTI), Three-dimensional conformal radiation treatment (3DCRT), Intensity-modulated radiation therapy (IMRT), Radiation treatment planning Background conformal radiotherapy (3DCRT) has been considered as Gliomas, which contain oligodendroglia, astrocytic and the standard therapy for patients with high-grade gliomas ependymal lesions are the most common primary intracra- and intensity-modulated radiotherapy (IMRT) is becoming nial tumors. High-grade gliomas, which make up 35 to 45% increasingly used to improve dose conformity and spare of all newly diagnosed primary brain tumors worldwide, critical normal tissues. However, the risk of radiation- have a very poor prognosis [1]. The three-dimensional induced brain injury increases with the increase of radi- ation dose [2-4]. The strenuous endeavor has been made to * Correspondence: [email protected] diminish radiation complications. Equal contributors With the assistance of conventional magnetic resonance Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China imaging (MRI) and planning computed tomography (CT) Ningxia Key Laboratory for Cerebrocranial Diseases, Yinchuan, China data, many critical intracranial structures, such as lens, Full list of author information is available at the end of the article © 2015 Wang et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. Radiation Oncology (2015) 10:64 Page 2 of 7 optic nerves and optic chiasm are well demarcated. How- 240 mm × 240 mm ,flipangle=90°,NEX=1,3mm thick- ever, it is difficult to accurately locate eloquent cortices ness). A block design paradigm (5 cycles, 30 sec on and and fiber connections in the white matter of the brain by 30 sec off) was utilized. Functional areas relevant to each routine neuroimaging. Excessive irradiation of eloquent treatment region were probed by Somatosensory tasks cortices and white matter fiber tracts is unavoidable. Blood (finger tapping with audio cue). Following the acquisition of oxygen level dependent functional magnetic resonance the functional data, gadolinium-enhanced high-resolution imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) images were acquired (TR/TE = 450/14, flip angle = 90°, have recently been used to identify the primary motor cor- matrix = 256 × 256, FOV = 240 mm × 240 mm ,and slice texes (PMCs) and corticospinal tracts (CSTs). These im- thickness 3 mm skip 0 mm). After the images were taken, aging techniques have been implemented in modern data were transferred to the Matlab workstation for analysis. neuronavigation systems and used to guide the surgical re- The DTI data acquisition sequence was a spin echo-echo moval of critically located intracranial lesions [5,6]. The planar imaging (SE-EPI) sequence with TR = 10,000 ms, purpose of our study was to evaluate whether the incorp- TE = 98.8 ms, acquisition matrix = 128 × 128 pixels; FOV = oration of BOLD-fMRI and DTI data into the 3D treat- 240 mm × 240 mm ; slice thickness = 3.0 mm. Diffusion- ment planning process could spare the healthy brain and weighted imaging with b factor of 1,000 mm /s was taken sensitive parts of the brain from high doses of radiation. along 25 noncollinear directions. The acquisition time of DTI sequence was 280 seconds. DTI data was analyzed on- Methods line by the advantage workstation of the MR scanner (AW Ethical Approval was obtained from the General Hospital 4.4). For CST analysis, a seed region of interest (ROI) and a of Ningxia Medical University Review Board and written target ROI were placed on the posterior limb of the internal informed consent was obtained from patients. The study capsule and pons (anterior blue portion on the color map). was conducted with strict adherence to the Declaration of Fiber tracking employed fractional anisotropy (FA) threshold Helsinki Principles. of 0.2 and a tract angular change of 30°. The color-coded FA maps were merged with the anatomical MRI images. Re- Subjects gions of interest were drawn on the fused FA maps. A total of 20 patients with high-grade gliomas adjacent The fused fMRI activation maps and the white matter to PMCs and CSTs between May 2012 and February tracts overlaid on the anatomical MRI volume were 2014 were recruited from the General Hospital of exported as separate grayscale dicom images and loaded Ningxia Medical University, China. Eleven male patients onto Pinnacle planning system software version 9.2 (Phi- and 9 female patients aged from 24 to 66 year-old were lips Medical Systems, Netherlands). The anatomical MRI enrolled in this study. images were registered with the CT volume for each pa- The glioma tissues in our study included 14 astrocyto- tient. Figure 1 shows the anatomical MRI images were mas (WHO Grade III) and 6 glioblastomas (WHO Grade IV). The bilateral PMCs and CSTs were located in the nor- mal regions without any overlapping with target volume of the lesions. BOLD-fMRI, DTI and conventional MRI were performed on patients (Karnofsky performance score ≥ 70) before radical radiotherapy treatment. Data acquisition and analysis Four different imaging studies were conducted in each patient: a planning CT for radiosurgery treatment and target tracking during radiation therapy treatment deliv- ering; an anatomical MRI to deliver a complete set of morphological MR data; a DTI to provide white matter tractography and a BOLD- fMRI to provide brain activa- tion maps. Axial CT images (3-mm slice thickness) were taken by a wide-bore Siemens Somatom Sensation Open CT scanner (Siemens, Germany). MRI volumes were ac- quired using a Signal HDx 3.0 T MRI scanner (General Electric Company, USA). BOLD fMRI data were obtained using fat-saturated Figure 1 T1-weighted MR imaging and the corresponding axial single-shotgradientechoplanarimaging (EPI) (TE=35ms, CT after registration. TR = 3,000 ms, acquisition matrix = 64 × 64 pixels, FOV = Wang et al. Radiation Oncology (2015) 10:64 Page 3 of 7 registered with the corresponding axial CT planes for a (GTV) was described as the operative cavity with any glioma case. remaining contrast-enhancing tissue on T1-weighted mag- netic resonance imaging or as unresected enhancing tumor. Treatment planning The initial clinical target volume (CTV1) was defined as the The target and organs at risk (OARs), i.e., optic nerves, T2 hyper intensity area (edema) with a 20 mm expansion. optic chiasm and brain stem were precisely described using An initial planning target volume (PTV1) was created by CT/anatomical MRI images. Both eyes were protected to adding a 30 mm expansion to the CTV1 to account for avoid beam damage during treatment planning. The PMCs setup uncertainties. A second clinical target volume (CTV2) and the CSTs situated near the target were defined by a was defined as the contrast enhancement region in T1 with radiologist and a neurosurgeon, using the tractography im- an additional 25 mm margin. A PTV2 was generated by ages and the fused activation maps. Gross tumor volume adding a 30 mm expansion to the CTV2. Figure 2 Axial isodose distribution in a patient with high-grade glioma. The A, B and C show the dose distributions for 3DCRT, IMRT and IMRT_ PMC&CST, respectively. (orange) ipsilateral PMC (red square symbol) contralateral PMC (pink square symbol) ipsilateral CST (green square symbol) contralateral CST. Wang et al. Radiation Oncology (2015) 10:64 Page 4 of 7 Table 1 Comparison of target volume coverage between For each case, three treatment plans were developed by 3DCRT and IMRT 3 different physicists using the Pinnacle planning system. 3DCRT IMRT tp The first physicist created conventional 3DCRT plans (3DCRT) and the PMCs and the CSTs situated near the PTV1 (50 Gy) target were not taken in account by the physicist. The tar- D (Gy) 65.06 ± 0.46 64.88 ± 0.66 1.461 0.160 max get and standard morphological OARs were considered in D (Gy) 59.78 ± 0.77 59.91 ± 0.85 −0.551 0.588 mean this plan. The second physicist developed IMRT plans CI 1.219 ± 0.054 1.071 ± 0.025 10.492 <0.001* (IMRT) and the PMCs and the CSTs situated near the tar- HI 0.210 ± 0.008 0.213 ± 0.012 −1.177 0.254 get were not considered by the physicist. The third physi- PTV2 (60 Gy) cist developed IMRT plans (IMRT_PMC&CST), and the PMCs and the CSTs situated near the target were consid- D (Gy) 65.06 ± 0.46 64.88 ± 0.66 1.461 0.160 max ered. Figure 2 shows the axial isodose distribution of a pa- D (Gy) 62.46 ± 0.39 62.36 ± 0.53 1.301 0.209 mean tient with high-grade glioma. CI 1.178 ± 0.082 1.055 ± 0.049 5.552 <0.001* The treatment plans met the requirement that at least HI 0.086 ± 0.022 0.082 ± 0.016 0.809 0.429 95% of the PTV receives the prescribed dose. Cumula- *Significant difference. tive doses to the lenses, optic nerves, optic chiasm, and brainstem were limited to a maximum dose of 54 Gy for the last three structures and as low as practically achiev- homogeneity, but IMRT displayed better PTV dose con- able for the former. For conventional 3DCRT treatment, formity. Regarding the comparison of PTV1 Dmax, the prescribed dose was 50 Gy to the PTV1, immediately PTV1 Dmean, PTV2 Dmax and PTV2 Dmean, there followed by 10 Gy to the PTV2, with a total cumulative was no significant difference between the 3DCRT and dose of 50 Gy to the PTV1 and 60 Gy to the PTV 2 both IMRT plans. The dosimetric details of brainstem, optic at 2 Gy per fraction. For IMRT plans, the prescribed chiasm, optic nerves, and lenses revealed no significant dose was 50 Gy to the PTV1 and 60 Gy to the PTV2, differences between the two plans and all of these organs which were delivered concurrently over 30 daily frac- were strictly maintained within the dose limitations. The tions, with a fractional dose of 2 Gy to the PTV2. Dmax and Dmean of PMCs and CSTs were observed in both 3DCRT and IMRT plans (Table 3); however no sig- Comparison criteria for the radiation treatment plans nificant difference was found between the two plans. The dose volume histograms (DVH) data were obtained from each patient. The dose coverage was analyzed accord- Comparison of target volume coverage and OAR sparing ing to the mean dose (Dmean), maximum dose (Dmax), con- between IMRT and IMRT_PMC&CST formity index (CI) and homogeneity index (HI). The CI was Treatment plan parameters are shown in Tables 4 and 5. defined as follows [7]: CI = VRI/PTV, where VRI represents According to the data presented, both PTV1 and PTV2 the volume covered by the prescription dose. A CI value of 1.0 indicates that the volume of the prescription isodose sur- face is equal to that of the PTV. The HI was defined as fol- Table 2 Comparison of OAR sparing between 3DCRT and lows [8]: HI = (D2 − D98)/D50, where Dx% represents the IMRT dose delivered to x% of the PTV. Lower HI values indicate a 3DCRT (Gy) IMRT (Gy) tp more homogeneous target dose. OARs (e.g., brainstem, optic Ipsilateral lens D 1.99 ± 1.00 2.67 ± 1.67 −1.938 0.068 max chiasm, optic nerves, and lenses) and PMCs and CSTs were Ipsilateral lens D 1.52 ± 0.75 1.98 ± 1.45 −1.454 0.162 mean compared based on the values of Dmax and Dmean. Contralateral lens D 1.71 ± 0.74 2.38 ± 1.97 −1.885 0.075 max Contralateral lens D 1.34 ± 0.55 1.84 ± 1.69 −1.585 0.129 mean Statistical analyses Ipsilateral optic nerve D 12.54 ± 17.85 12.32 ± 13.38 0.156 0.877 The comparison of parameters between different plans was max analyzed by the paired two-tailed Student t test. Differences Ipsilateral optic nerve D 8.55 ± 11.99 8.57 ± 9.40 −0.014 0.989 mean were considered statistically significant at p < 0.05. Contralateral optic 7.55 ± 8.94 7.02 ± 7.68 1.025 0.318 nerve D max Results Contralateral optic 5.14 ± 5.92 4.59 ± 4.76 1.364 0.188 nerve D Comparison of target volume coverage and OAR sparing mean between 3DCRT and IMRT Optic chiasm D 12.53 ± 15.50 12.76 ± 13.53 −0.241 0.812 max Parameters related to dose coverage planning for Optic chiasm D 9.22 ± 11.64 8.28 ± 8.70 1.060 0.302 mean 3DCRT and IMRT are presented in Tables 1 and 2. The Brainstem D 14.78 ± 14.77 14.04 ± 11.62 0.523 0.607 max results indicated that there was no significant difference Brainstem D 7.09 ± 8.31 6.52 ± 6.99 0.711 0.486 mean between the 3DCRT and IMRT plans in terms of dose Wang et al. Radiation Oncology (2015) 10:64 Page 5 of 7 Table 3 Comparion of radiation dose between 3DCRT and Table 5 Comparison of OAR sparing between IMRT and IMRT IMRT_PMC&CST 3DCRT (Gy) IMRT (Gy) tp IMRT (Gy) IMRT_PMC&CSTtp (Gy) Ipsilateral PMC D 46.50 ± 8.65 46.54 ± 7.77 −0.050 0.960 max Ipsilateral lens D 2.67 ± 1.67 2.76 ± 1.64 −1.574 0.132 max Ipsilateral PMC D 28.45 ± 7.78 27.67 ± 8.06 1.429 0.169 mean Ipsilateral lens D 1.98 ± 1.45 2.03 ± 1.50 −1.294 0.211 mean Contralateral PMC D 24.86 ± 9.89 21.40 ± 10.94 1.542 0.140 max Contralateral lens D 2.38 ± 1.97 2.43 ± 1.95 −1.063 0.126 max Contralateral PMC D 14.73 ± 6.02 14.11 ± 7.57 0.390 0.701 mean Contralateral lens 1.84 ± 1.69 1.89 ± 1.72 −0.940 0.359 Ipsilateral CST D 51.26 ± 4.24 50.61 ± 4.72 1.801 0.088 max mean Ipsilateral CST D 36.51 ± 6.63 36.06 ± 7.57 0.893 0.383 mean Ipsilateral optic nerve 12.32 ± 13.38 12.44 ± 13.91 −0.599 0.556 Contralateral CST D 35.64 ± 10.15 36.11 ± 10.05 −0.859 0.401 max max Ipsilateral optic nerve 8.57 ± 9.40 8.78 ± 10.08 −1.126 0.274 Contralateral CST D 20.97 ± 7.43 18.90 ± 7.45 1.454 0.162 mean mean Contralateral optic 7.02 ± 7.68 7.07 ± 7.71 −0.353 0.728 nerve D max (Dmax, Dmean, CI and HI) were analyzed and showed no significant differences between two groups. The Dmax Contralateral optic 4.59 ± 4.76 4.66 ± 4.95 −0.729 0.475 nerve D mean and Dmean to these conventional OARs (e.g., brainstem, Optic chiasm D 12.76 ± 13.53 12.49 ± 13.20 1.488 0.153 optic chiasm, optic nerves, and lenses) showed no signifi- max cant differences between the two plans. The Dmax to the Optic chiasm D 8.28 ± 8.70 8.20 ± 8.63 0.573 0.573 mean ipsilateral and contralateral PMC and CST regions was Brainstem D 14.04 ± 11.62 13.56 ± 11.08 1.260 0.223 max considerably decreased by 28.7%, 24.5%, 20.2% and 37.6%, Brainstem D 6.52 ± 6.99 6.46 ± 7.05 0.790 0.439 mean respectively. The Dmean to the ipsilateral and contralat- eral PMC and CST regions was considerably decreased by 27.8%, 30.4%, 23.1% and 33.4%, respectively (Table 6). The DTI and BOLD-fMRI have recently been used to identify the white-matter pathways and functional struc- tures of the brain. In our previous study, we proposed a Discussion clinically feasible protocol of integrating BOLD-fMRI Radiation therapy is commonly applied to the brain tu- and DTI to optimize the extent of resection involving mors due to its ability to control cell growth; however, the cortical motor areas and subcortical white matter radiation therapy can have detrimental effects on the tracts in patients with brain gliomas. Those information central nervous system causing neurological complica- helped neurosurgeons resected the maximum amount of tions. The response of cerebral tissue to radiation can tumor while still preserving the most critical cortices of lead to the deficits in neural functions [9,10]. The extent the brain, thus resulting in enhanced postoperative quality of neurologic deficit is associated with the location and of life for patients [13]. The incorporation of this informa- size of radiation-induced brain injury [11,12]. Efforts tion for radiosurgery planning has also been suggested. dedicated to the precise division of brain lesions have Liu et al. has reported a novel method to integrate the been made to reduce the risk of neurological complica- fMRI brain activation map with treatment planning for tions caused by the radiation therapy. stereotactic radiosurgery (SRS). Direct irradiation of the eloquent cortices was avoided by multiple radiation arcs Table 4 Comparison of target coverage between IMRT or static radiation beams in SRS planning, and the average and IMRT_PMC&CST Table 6 Comparion of radiation doses betweeen IMRT IMRT IMRT_PMC&CST tp and IMRT_PMC&CST PTV1 (50 Gy) IMRT (Gy) IMRT_PMC& tp D (Gy) 64.88 ± 0.66 65.04 ± 0.70 −0.806 0.430 CST (Gy) max D (Gy) 59.91 ± 0.85 59.85 ± 0.68 0.633 0.534 Ipsilateral PMC D 46.54 ± 7.77 33.20 ± 11.13 7.304 <0.001 mean max CI 1.071 ± 0.025 1.073 ± 0.024 −1.077 0.295 Ipsilateral PMC D 27.67 ± 8.06 19.99 ± 8.78 7.150 <0.001 mean HI 0.213 ± 0.012 0.209 ± 0.016 0.911 0.374 Contralateral PMC D 21.40 ± 10.94 16.16 ± 9.07 5.250 <0.001 max PTV2 (60 Gy) Contralateral PMC D 14.11 ± 7.57 9.82 ± 5.62 5.276 <0.001 mean D (Gy) 64.88 ± 0.66 65.04 ± 0.70 −0.806 0.430 Ipsilateral CST D 50.61 ± 4.72 40.37 ± 6.55 9.233 <0.001 max max D (Gy) 62.36 ± 0.53 62.41 ± 0.56 −0.287 0.777 Ipsilateral CST D 36.06 ± 7.57 27.72 ± 8.87 8.032 <0.001 mean mean CI 1.055 ± 0.049 1.039 ± 0.047 1.643 0.117 Contralateral CST D 36.11 ± 10.05 22.52 ± 10.36 6.959 <0.001 max HI 0.082 ± 0.016 0.089 ± 0.016 −1.646 0.116 Contralateral CST D 18.90 ± 7.45 12.59 ± 5.51 6.362 <0.001 mean Wang et al. Radiation Oncology (2015) 10:64 Page 6 of 7 dose reduction to the eloquent cortices was 32% [14]. In Abbreviations BOLD-fMRI: Blood oxygen level dependent functional magnetic resonance addition, it has been reported that the risk of radiation- imaging; DTI: Diffusion tensor imaging; 3DCRT: Three-dimensional conformal induced neuropathy was minimized by the integration of radiation treatment; PMCs: Primary motor cortexes; CSTs: Corticospinal tracts; tractography of the brain white matter with DTI into radi- CT: Computed tomography; OARs: Organs at risk; IMRT: Intensity-modulated radiation therapy; IMRT_ PMC&CST: Intensity-modulated radiotherapy ation treatment planning of radiosurgery using Gamma planning with PMC and CST information; WHO: World Health Organization; Knife [15]. Moreover, Pantelis et al. has demonstrated that MRI: Magnetic resonance imaging; SE-EPI: Spin echo-echo planar imaging; critical structures of brain could be marked and spared ROI: Region of interest; GTV: Gross tumor volume; CTV1: Initial clinical target volume; PTV1: Initial planning target volume; CTV2: Second clinical target with the aid of the integration of BOLD-fMRI and DTI volume; PTV2: Second planning target volume; DVHs: Dose volume into CyberKnife stereotactic radiosurgery [16]. histograms; Dmax: The maximum dose; Dmean: Mean dose; CI: Conformity In this study, BOLD-fMRI and DTI were used to localize index; HI: Homogeneity index. the bilateral PMCs and CSTs and the information obtained Competing interests from these two technologies were integrated into radiation The authors declare that they have no competing interests. treatmentplanning.The firstpartofour study (3DCRT versus IMRT) indicated that there was no significant Authors’ contributions XDW, HCX, XYH and XXJ conceived the study and draft the manuscript. reduction in the dose to bilateral PMCs and CSTs between MLW and XDW performed the statistical analysis and drafted the manuscript. the 3DCRT and IMRT plans. The critical structures adja- HM, YHG, XSX, YLG and HH participated in the analysis of the treatment of cent to the target volume marked as OARs can be better radiotherapy plans and draft this manuscript. YX edited this manuscript. All authors read and approved the final manuscript. spared during the IMRT planning process due to a steep dose gradient and a high conformity [17,18]. The second Acknowledgements part of our study (IMRT versus IMRT_ PMC&CST), has This work was supported by the Natural Science Foundation of China (Grant No. 81260373) and the Natural Science Foundation of Ningxia shown that a significant reduction in the dose to bilateral (Grant No. NZ11269). PMCs and CSTs regions can be achieved without com- promising the coverage of planning target volume and the Author details Department of Radiology, General Hospital of Ningxia Medical University, limiting dose to these conventional OARs. Yinchuan, China. Ningxia Key Laboratory for Cerebrocranial Diseases, Sparing of the bilateral PMCs and CSTs does not repre- Yinchuan, China. Department of Neurosurgery, General Hospital of Ningxia sent any significant breakthrough in the treatment of brain Medical University, Yinchuan, China. Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, China. Department tumors, but we have demonstrated that it is feasible to re- of Radiology, Xi’an NO.1 Hospital, Xi’an, China. Tissue Organ Bank & Tissue duce the irradiation of critical structures adjacent to the Engineering Centre, General Hospital of Ningxia Medical University, Yinchuan, target volume. The development of the most appropriate Ningxia, China. Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin IMRT plan for the patient could be achieved by the identi- Grove, QLD, Australia. fication of the important functional structures of the brain tissues proximal to the tumors. Sparing these vital func- Received: 28 October 2014 Accepted: 19 February 2015 tional structures is important to maintain quality of life, even in those patients with restricted life expectancy. The References current study has shown that the DTI examination and 1. Chang J, Narayana A. Functional MRI for radiotherapy of gliomas. Technol MR Spectroscopy are valuable tools to differentiate the Cancer Res Treat. 2010;9(4):347–58. 2. Bleehen NM, Stenning SP. A Medical Research Council trial of two postoperative recurrent glioma from the radiation injury radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The for patients with a glioma [19,20]. Medical Research Council Brain Tumour Working Party. Br J Cancer. We are currently investigating paradigms for Broca’s 1991;64(4):769–74. 3. Butler JM, Rapp SR, Shaw EG. Managing the cognitive effects of brain tumor and Wernicke’s areas (speech center), Broadmann-17 radiation therapy. Curr Treat Options Oncol. 2006;7(6):517–23. functional structures (visual center) and optic tracts. 4. Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: The application of the fMRI in low grade cases has also current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995;31(4):983–98. been validated. 5. Kamada K, Todo T, Masutani Y, Aoki S, Ino K, Takano T, et al. Combined use of tractography-integrated functional neuronavigation and direct fiber Conclusions simulation. J Neurosurg. 2005;102(4):664–72. 6. Pirotte B, Voordecker P, Neuroschl C, Baleriaux D, Wikler D, Metens T, et al. In conclusion, integration of BOLD-fMRI and DTI into Combination of functional magnetic resonance imaging-guided radiation treatment planning is feasible and beneficial. neuronavigation and intraoperative cortical brain mapping improves With the assistance of the above-described techniques, the targeting of motor cortex stimulation in neuropathic pain. Neurosurgery. 2008;62(6 Suppl 3):941–56. structures adjacent to suspicious cancerous lesions could 7. Feuvret L, Noël G, Mazeron JJ, Bey P. Conformity index: a review. Int J Radiat be clearly marked as OARs and spared during treatment. Oncol Biol Phys. 2006;64(2):333–42. However, a wider investigation and the longer-term 8. Hodapp N. The ICRU report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT). Strahlenther clinical follow up are required to further validate the Onkol. 2012;188(1):97–9. effect of the integration of BOLD-fMRI and DTI on spar- 9. Keime-Guibert F, Napolitano M, Delattre JY. Neurological complications of ingnormaltissues. radiotherapy and chemotherapy. J Neurol. 1998;245(11):695–708. Wang et al. Radiation Oncology (2015) 10:64 Page 7 of 7 10. DeAngelis LM, Delattre J-Y, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989;39(6):789–96. 11. Flickinger JC, Kondziolka D, Lunsford LD, Kassam A, Phuong LK, Liscak R, et al. Development of a model to predict permanent symptomatic postradiosurgery. Int J Radiat Oncol Biol Phys. 2000;46(5):1143–8. 12. Voges J, Treuer H, Sturm V, Büchner C, Lehrke R, Kocher M, et al. Risk analysis of linear accelerator radiosurgery. Int J Radiat Oncol Biol Phys. 1996;36(5):1055–63. 13. Jia XX, Yu Y, Wang XD, Ma H, Zhang QH, Huang XY, et al. fMRI-driven DTT assessment of corticospinal tracts prior to cortex resection. Can J Neurol Sci. 2013;40(4):558–63. 14. Liu WC, Schulder M, Narra V, Kalnin AJ, Cathcart C, Jacobs A, et al. Functional magnetic resonance imaging aided radiation treatment planning. Med Phys. 2000;27(7):1563–72. 15. Maruyama K, Kamada K, Shin M, Itoh D, Aoki S, Masutani Y, et al. Integration of threedimensional corticospinal tractography into treatment planning for gamma knife surgery. J Neurosurg. 2005;102(4):673–7. 16. Pantelis E, Papadakis N, Verigos K, Stathochristopoulou I, Antypas C, Lekas L, et al. Integration of functional MRI, white matter tractography in stereotactic radiosurgery clinical practice. Int J Radiat Oncol Biol Phys. 2010;78(1):257–67. 17. Moretto F, Rampino M, Munoz F, Ruo Redda MG, Reali A, Balcet V, et al. Conventional 2D (2DRT) and 3D conformal radiotherapy (3DCRT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer treatment. Radiol Med. 2014;119(8):634–41. 18. Arbea L, Ramos LI, Martinez-Monge R, Moreno M, Aristu J. Intensity- modulated radiation therapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC): dosimetric comparison and clinical implications. Radiat Oncol. 2010;5:17. 19. Xu JL, Li YL, Lian JM, Dou SW, Yan FS, Wu H, et al. Distinction between postoperative recurrent glioma and radiation injury using MR diffusion tensor imaging. Neuroradiology. 2010;52(12):1193–9. 20. Rabinov JD, Lee PL, Barker FG, Louis DN, Harsh GR, Cosgrove GR, et al. In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience. Radiology. 2002;225(3):871–9. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit

Journal

Radiation Oncology – Springer Journals

Published: Dec 1, 2015

Keywords: cancer research; oncology; radiotherapy; imaging / radiology

There are no references for this article.