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Year : 2019  |  Volume : 15  |  Issue : 1  |  Page : 223-230

Commissioning of portal dosimetry using a novel method for flattening filter-free photon beam in a nontrue beam linear accelerator

1 Department of Radiation Oncology, Yashoda Hospitals, Hyderabad, Telangana; Research and Development Centre, Bharathiar University, Coimbatore, Tamil Nadu, India
2 Research and Development Centre, Bharathiar University, Coimbatore, Tamil Nadu; Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiation Oncology, Yashoda Hospitals, Hyderabad, Telangana, India

Date of Web Publication13-Mar-2019

Correspondence Address:
Dr. Subramani Vellaiyan
All India Institute of Medical Sciences, Ansari Nagar East, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1181_16

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 > Abstract 

Aim: The aim of this study is to commission and validate the portal dosimetry (PD) system using an indirect method for flattening filter free (FFF) photon beam of the upgraded c-series linear accelerator.
Background: Varian Medical System clinacs with amorphous-silicon portal imager panel (aSi-1000) do not have PD for FFF beams. Recently, our c-series linear accelerator was upgraded to deliver 6MV FFF (6MVFFF) photon beam with the highest dose rate of 1400 monitor unit (MU)/min. The study, therefore, focuses on the commissioning and validation of PD for the 6MVFFF beam.
Materials and Methods: An indirect method was implemented to predict the portal dose for FFF beam in Eclipse as the treatment planning system does not have direct prediction algorithm for FFF beam (version. 11). Dosimetrical characteristics of aSi-electronic portal imaging device (EPID) were evaluated for 6MVFFF beam and validation of PD for 6MVFFF beam was performed for open fields along with pretreatment quality assurance of intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS) techniques for 30 patients planned with 6MVFFF beam.
Results: ASi-EPID saturates between 100 and 130 cm source to detector distance (SDD) for 6MVFFF beam and resolved at more than 140 cm SDD. The squared correlation coefficient (R2) for MU linearity was found to be 1 (R2 = 1), and instantaneous dose response linearity at different SDD's was found to be 0.999 (R2 = 0.999) for the 6MVFFF beam. Maximum gamma area index (GAI) for 3% dose difference and 3 mm distance-to-agreement criteria for IMRT, VMAT, and SRS/stereotactic radiotherapy plans was 97.9% ± 0.3%, 96.3% ± 0.5%, and 98.2% ± 0.2%, respectively.
Conclusion: The results reveal that this novel method can be used to commission portal dosimetry for 6MVFFF beam as it is a convenient, faster, and accurate method.

Keywords: ASi-electronic portal imaging device, flattening filter free beam, portal dosimetry, volumetric-modulated arc therapy

How to cite this article:
Gandhi A, Vellaiyan S, Subramanian V S, Shanmugam T, Murugesan K, Subramanian K. Commissioning of portal dosimetry using a novel method for flattening filter-free photon beam in a nontrue beam linear accelerator. J Can Res Ther 2019;15:223-30

How to cite this URL:
Gandhi A, Vellaiyan S, Subramanian V S, Shanmugam T, Murugesan K, Subramanian K. Commissioning of portal dosimetry using a novel method for flattening filter-free photon beam in a nontrue beam linear accelerator. J Can Res Ther [serial online] 2019 [cited 2020 Sep 18];15:223-30. Available from: http://www.cancerjournal.net/text.asp?2019/15/1/223/241956

 > Introduction Top

The success of high dose conformal therapy techniques depends critically on the accuracy of treatment delivery. The recent introduction of un-flattened photon beams (flattening filter free, [FFF]) to c-series linear accelerator (clinac) has raised the need to develop or to adapt the quality assurance (QA) methods to the new situation. Pretreatment verification is a crucial step in ensuring accurate treatment delivery due to the number of uncertainties in the planning process. Most widely used a form of pretreatment QA for volumetric-modulated arc therapy (VMAT) generally consists of absolute dose measurements (with an ionisation chamber, diode, thermoluminescent dosimeters, etc.) combined with planar isodose distribution measurements in a phantom (with film, two-dimensional [2D] detector array, etc.). The process of acquiring data, data handling, and analysis are time-consuming and laborious task in planar dose verification.

The introduction of the electronic portal imaging device (EPID) helped to overcome the issues with conventional film dosimetry and 2D detector array.[1],[2] In addition, portal dosimetry using EPID is an attractive method to perform pretreatment QA because of its prompt setup, easy data acquisition, and high spatial resolution.[3],[4] The pre-treatment QA time for planar dosimetry can further be reduced with portal dosimetry for the 6MVFFF beam.[5] The FFF beam is used mainly in stereotactic treatments to shorten the treatment time which uses large monitor units (MUs).[6] Varian amorphous-Silicon (aSi) EPID portal dosimetry system (Varian Medical System, Palo Alto, CA, USA) for flattening filtered (FF) beam is a well-proven QA tool for routine intensity-modulated radiation therapy (IMRT) and VMAT using pretreatment QA due to its incorporation in Eclipse treatment planning system (TPS).[7] However, the portal dosimetry has the limitation for FFF beam, due to its higher dose rate which saturates aSi-EPID at the routine source to detector distance (SDD = 100 cm) and straight forward PD prediction is not available in Eclipse TPS (v. 11) for nontrue beam linear accelerator. In the present study, first an indirect method was implemented to commission the PD in an upgraded c-series clinac. Second, the validation of PD was performed regarding dosimetrical characteristics of aSi-EPID, open-field dosimetry, and MLC test pattern for 6MVFFF beam. Finally, pretreatment QA was performed for IMRT, VMAT, stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) for 30 patients using 6MVFFF beams.

 > Materials and Methods Top

System overview

The EPID used in our study is a commercially available aSi imaging device (aS1000 from Varian Medical Systems, Palo Alto California, USA) mounted on a Clinac 2100 C/D (photon energies of 6 and 15 MV) with 120 leaves dynamic MLC (Varian Medical Systems). Recently, c-series linac machine had been upgraded to deliver 6MVFFF (TPR 20, 10 = 0.6336 ± 0.005) beam along with the existing 6 MV and 15 MV nominal energies. The EPID system includes, (i) an image detection unit, consist of the detector and accessory electronics, (ii) an image acquisition unit (IAS3), contains drive and acquisition electronics and interfacing hardware, and (iii) an integrated workstation with TPS (portal dosimetry). The aS1000 EPID detector system is mounted on the robotic support arm called E-arm, which uses mechanical breaks for placing the detector to an accurate and reproducible position. The E-arm allows the detector to be positioned at 95–180 cm from the radiation focus point and the detector has a 40 cm × 30 cm active imaging area at 100 SDD. The aS1000 has an active imaging area with 1024 × 768 pixel matrix. The EPID has a pixel resolution of 0.39 mm and is capable of capturing 14-bit images at 30 fps (frames per se cond) with IAS3.

Method to commission portal dosimetry in c-series clinac

Portal dosimetry configuration for flattening filter free beam in upgraded clinac

Portal dosimetry was configured in clinac using SRS mode for FFF beam. SRS mode was reprogrammed to enable the acquisition of portal dose for the 6MVFFF beam. The EPID for portal dosimetry required dosimetry calibration in several steps. In the first step, imager was calibrated with dark and flood field to correct the background signal and to get the uniform pixel gain. Beam profile correction for nonuniform X-ray beam intensity was then introduced by providing the diagonal profile of larger field size.

SDF: Darkfield signal acquired without radiation to the background noise.

SFF: Flood field signal acquired by uniformly irradiating the entire active are of the EPID for pixel gain correction.

Sraw: Raw signal acquired by the EPID for portal dosimetry.

The second step is dose normalization, which converts the measured signals to the radiation dose using a reference condition, normally defined as the calibration unit (CU) by the digital signals per MU. After dose normalization, the measured dose images are generated by converting the EPID signals into the CU, which can then be compared to the predicted dose images. All calibrations and measurements were performed at a source-to-imager distance (SDD) of 150 cm to avoid detector saturation.

Portal dose image prediction algorithm commissioning for flattening filter free beam in treatment planning system

Before portal dosimetry commissioning in TPS, a replica machine has been created, and anisotropic analytical algorithm (AAA) was commissioned for 6MVFFF beam using 6MVFF (nominal 6MV FF) empty template. The flattening filter option was changed to “NONE” to avoid its presence in the beam data calculation. The replica machine was approved, and portal dose image prediction (PDIP) algorithm was commissioned onto the same machine. PDIP algorithm is used only for the portal dose prediction purpose and predicted images are absolutely scaled regarding CU in TPS. The PDIP algorithm was commissioned in Eclipse planning system for FFF beam by giving the input data (an intensity profile, the definition of output factors specific to the imager, dosimetric images acquired for calibration fluence and an actual fluence) of FFF beam parameters to the 6MVFF PDIP algorithm template.

Dosimetric characteristic of aSi-electronic portal imaging device for flattening filter free beam

Monitor unit linearity

The linearity of the detector response as a function of MUs was investigated by delivering 5–1500 MUs for 10 cm × 10 cm field size. The average CU value of 1 cm × 1 cm matrix at the portal dose image at beam axis was taken for analysis. Similar measurements were carried out with an ion chamber (FC65G) in water phantom for comparison. A range of MU was chosen to cover the clinical IMRT, VMAT, and VMAT based stereotactic plans. The squared correlation coefficient was used to analyze the linearity function of aSi-EPID and ion chamber.

Detector saturation

The detector saturates under two situations. First, during the calibration process of the EPID where the flood field acquired can be saturated and second, during the dosimetric measurements. The detector saturation was investigated to find the suitable SDD for portal dosimetry for 6MVFF beam, and it was positioned at 100, 110, 120, 130, 140, and 150 cm SDDs for different MU sets and PD images were acquired. The profiles and CU value of PD image at beam axis were analyzed in portal dosimetry workspace.

Dose rate response

The linearity due to variations in the dose rate was investigated by measuring the average CU at the beam axis (1 cm × 1 cm matrix) of dose image for a static field size of 10 cm × 10 cm, same MU (100 MU) but varying the detector distance from the source to invoke inverse square law. The detector distance used is 150, 155, 160, 165, 170, 175, and 180 cm from the source.

Field size dependence

The response of the aSi-EPID for various field sizes was evaluated. Field sizes ranging from 3 cm × 3 cm to 20 cm × 20 cm were exposed to a dose of 100 MU, and respective CU was measured at the beam axis for 5 mm × 5 mm matrix. Similar measurements were carried out with an ion chamber (FC65G, iba dosimetry) placed in a water phantom at the depth of 1.5 cm for comparison. All the readings were normalized to 10 cm × 10 cm field size.

Gantry rotational stability

The mechanical stability of the detector for portal dosimetry was assessed for different gantry angles as the support arm; gantry sag could impact the image center due to the detector displacement during rotation. This test was performed by acquiring a PD image for 15 cm × 15 cm field size at gantry 0° which was kept as a reference.[4] The same PD image of 15 cm × 15 cm field size was acquired at 0°, 30°, 60°, 90°, 120°, 150°, 180°, 330°, 300°, 270°, 240°, and 210° and compared with reference image in omnipro accept software after converting the data to ascii format to find the accurate PD image center.

Validation of portal dosimetry for open fields and test patterns

Seven open fields and test pattern (pyramid shape) were selected and validated for PD using FFF beams. The validation was based on gamma analysis, CU at beam axis for open fields. The field sizes were selected in the range of 3 cm × 3 cm to 15 cm × 15 cm. The measurements were performed with aSi-EPID at SDD = 150 cm for all fields. The acquired images were then compared to predicted images for 2% dose difference (DD) and 2 mm distance-to-agreement (DTA) criteria.

Validation of portal dosimetry for intensity-modulated radiation therapy, volumetric-modulated arc therapy, and stereotactic radiosurgery using flattening filter free beam-quality assurance plan creation and delivery

The original clinical treatment plans were created for 30 patients using IMRT, VMAT, SRS, and SRT techniques with 6MVFFF beams. The original treatment plan with FFF beams cannot be used for direct portal dosimetry prediction as Eclipse TPS version 11 does not have an inbuilt algorithm for FFF beam portal dose prediction. A QA plan was created by first copying the original 6MVFFF treatment plan, then replacing the energy of the FFF beam with the same nominal energy of the FF (6MVFF) beam in the replica machine while ensuring that the FF beam parameters are replaced carefully with the FFF beam parameters in the commissioning workspace. This QA plan was used to predict the portal dose in TPS.

On the other hand, the portal dose images were acquired in the integral mode for the clinical 6MVFFF plan using aSi-EPID at 150 cm. The acquired PD image can be tagged with the QA plan for analysis by simple dose plane export function in portal dosimetry workspace [Figure 1].
Figure 1: Work flow of portal dosimetry for 6MV flattening filter free beam in treatment planning system

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Gamma analysis is well established as a method of quantitatively comparing dose distributions, either measured or calculated. Gamma evaluation provides single value (gamma area index) evaluating both distance and DD agreement. The gamma area index (GAI) was computed using acceptance criteria of 3% DD and 3 mm DTA.

 > Results Top

Dosimetric characteristic of aSi-electronic portal imaging device for flattening filter free beam

Monitor unit linearity

The linearity of the detector response and ion chamber regarding MU is illustrated in [Figure 2]. The slope of the trend line curve of MU linearity is 0.004 and 0.019 and R2 = 1.000 for both for aSi-EPID and the ion chamber, respectively. The measured PD is proportional to the number of MUs, for entire measured range from 5 to 1500 MUs and for <25 MU the measured PD is within 10% of the expected value due to the lack of signal, whereas >30 MU, it is within 2% of the expected value.
Figure 2: (a) Graphical plot of monitor unit linearity of aSi-electronic portal imaging device (b) monitor unit linearity of ion chamber

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Detector saturation

[Figure 3] reveals the impact of the saturation of the aSi-EPID as a function of CU, for both in line and cross line profiles. There were severe signal loss of more than −30% in 100, 110, 120, and 130 cm SDD for all MU set where at 140 and 150 cm SDD, the detector did not saturate and was found to be suitable working SDD for portal dosimetry for 6MVFFF beam at the dose rate of 1400 MU/min.
Figure 3: The saturation of the aSi-electronic portal imaging device reading as a function of dose rate. (a) Data are shown for a 15 cm × 15 cm field at source to detector distance = 100 cm and source to detector distance = 150 cm (b) source to detector distance = 110 cm and 150 cm (c) source to detector distance = 120 and 150 cm (d) source to detector distance = 130 cm and 150 cm (e) source to detector distance = 140 cm and 150 cm (f) aSi-electronic portal imaging device saturation plot as a function of monitor unit and source to detector distance

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Dose rate response

The images were obtained at different SDD's delivering 100 MU at a repetition rate of 1400 MU/min. These images were analyzed and the mean value of the central 1 cm × 1 cm pixel at beam axis region was measured and plotted [Figure 4]. The distance from the source to the detector gives an inverse square factor which was used to plot a graph against CU. A linear regression analysis produced a coefficient of determination R2 = 0.9999.
Figure 4: Inverse square law behaviour, measured for a field size of 10 cm × 10 cm with the aSi-electronic portal imaging device by varying source to detector distance

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Field size dependence

The field size dependence of aSi-EPID was compared to the dose measured with an ion chamber in a water phantom. The aSi-EPID signal was compared to ion chamber readings normalized to the field size of 10 cm × 10 cm as shown in [Figure 5]. The field size response relative to the ion chamber is −6% for a 3 cm × 3 cm field and + 2.1% for a 20 cm × 20 cm field.
Figure 5: Field size response of the electronic portal imaging device. The normalized electronic portal imaging device signal is compared to normalized ion chamber signal (charge) at 1.5 cm depth in a water phantom

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Gantry rotation stability

Mechanical stability of the detector was assessed for different gantry angles. A visual profile comparison was performed in omnipro accept (iba dosimetry, Germany) analyze software for all angles against 0°. All the profiles were falling on the reference profile [Figure 6]. The maximum variation of 1.4% was found in aSi-EPID signal at gantry angle of 120°.
Figure 6: (a) Profile analysis of gantry rotation stability. (b) Plot between aSi-electronic portal imaging device signal and gantry angle

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Validation of portal dosimetry for open fields and test pattern

Portal dose images of open fields and test pattern were acquired to validate the accuracy of the portal dose prediction algorithm. The mean gamma area index (GAI) was found to be 98.7 ± 0.5 for open fields and GAI was found to be 99.1 ± 0.5 for test pattern [Figure 7] for 2% DD and 2 mm DTA criteria. The maximum CU deviation was found in 3 cm × 3 cm field size.
Figure 7: Comparison of predicted and measured pyramid-shaped test fluence pattern for 6MV flattening filter free beam

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Validation of portal dosimetry for intensity-modulated radiation therapy, volumetric-modulated arc therapy, and stereotactic radiosurgery using flattening filter free beam

Portal dose was predicted for all 30 patients in the replica machine in TPS. Portal dosimetry was performed using original plan at 150 cm SDD, and the same was exported in text format (*.dxf) to the replica machine. The GAI was calculated for 3% DD and 3 mm DTA criteria [Table 1]. The maximum variation found was 97.9% ± 0.3%, 96.3% ± 0.5%, and 98.2% ± 0.2% for IMRT, VMAT, and SRS/SRT plans, respectively [Figure 8].
Table 1: The GAI (3% dose differences, 3 mm distance to agreement) for 30 intensity modulated radiotherapy, volumetric-modulated arc therapy, stereotactic radio surgery and stereotactic radio therapy patient plans done with 6MV flattening filter free beam

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Figure 8: Portal dosimetry of intensity modulated radiation therapy, Rapidarc and stereotactic radiosurgery plan

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 > Discussion Top

The validation of the aSi-EPID was performed for the 6MVFFF beam, regarding dosimetrical characteristic and its efficacy for portal dosimetry. To resolve the current limitation of the portal dosimetry restricted to FF beams in Eclipse TPS, we proposed a practical approach that can be used to do portal dosimetry with FFF beams without any third party software. Our method is compared to other authors' for the same region. Min et al., described a method to implement portal dosimetry for FFF beam by replacing the FFF beams with FF beams of the same nominal energy, reducing the dose rate to avoid the saturation effect of the EPID detector; and adjust the total MU to match the gantry and MLC leaf motions.[8] In this study, it is integrated into the existing portal dosimetry system without the need for any additional image processing, dose rate reduction, alteration of MU, and transfer to other system. Thus, it has become highly efficient in clinical routine. Validation of portal dosimetry was performed and reported by many authors for 6MVFF beam using aSi-EPID.[1],[2],[5],[9],[10] The study results exhibits the same pattern as the other authors' study regarding dosimetrical characteristics.[1],[2],[3],[5],[9],[10] The dosimetrical characteristics of portal imager shows that it has a good dosimetric response for FFF beams at suitable SDD as the similar study was done by Nicolini et al. The deviation of PD image center, particularly for smaller field size, due to cassette sag can be corrected in portal dosimetry workspace either automatically or manually. Portal dosimetry for large fields could be the issue with SDD = 150 cm for the 6MVFFF beam. The behavior of aSi-EPID for field size dependence differed slightly from that of an ion chamber measurement in water phantom and hence, it is useful for relative dosimetry.[11] Although the performance of the aSi-EPID detector for 6MVFFF is not equivalent to a dose to water measurement, it can be used effectively to verify the complex fluence of different treatment techniques.[6],[12] The PDIP commissioning accuracy was checked with the test pattern plan and found that it passed in the gamma analysis with 2% DD and 2 mm DTA criteria. It was expected to pass with 1% DD and 1 mm DTA criteria since the same test pattern was used to create the kernel during PDIP algorithm commissioning in TPS. The maximum dose rate of 1400 MU/min was used to create clinical plans and portal dosimetry was performed using 6MVFFF beam. A good agreement between predicted and measured PD is observed on patient-specific QA data set for different treatment techniques and the gamma area index (GAI) was very well within the tolerance limit.[13],[14] Renormalization method (relative) was used in some cases where the dose gradient was high.[14] The maximum standard deviation of the mean GAI was ±1.8, since the clinical plan was performed with high degree of modulation using IMRT technique and the minimum was ±0.1 for SRS plan.

However, this proposed method is little laborious in some scenarios where the portal dosimetry is used routinely for the nominal 6MVFF beam regarding verification of calibration file replacement before the use of portal dosimetry. In our suggested approach, the QA plan is not on the same machine where the actual plan was done. The difficulty from commissioning side would be mainly the editing of dose rate file of SRS mode in the image calibration in clinac and switch over to regular FF beam image calibration. Two separate calibration file folders were kept for ease routine use which includes dark field, flood field, beam profile correction, and dose normalization files. This study does not include the effect of changing the flattening filter status in AAA algorithm.

 > Conclusion Top

In this study, commissioning and validation of portal dosimetry were performed for 6MVFFF beam using a novel method in an upgraded linear accelerator. The overall results demonstrate that the new method can be utilized to commission portal dosimetry using aSi 1000 for FFF beams and it is a convenient, faster, and accurate method when it is integrated into the same clinical network.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

van Elmpt W, McDermott L, Nijsten S, Wendling M, Lambin P, Mijnheer B, et al. Aliterature review of electronic portal imaging for radiotherapy dosimetry. Radiother Oncol 2008;88:289-309.  Back to cited text no. 1
Van Esch A, Depuydt T, Huyskens DP. The use of an aSi-based EPID for routine absolute dosimetric pre-treatment verification of dynamic IMRT fields. Radiother Oncol 2004;71:223-34.  Back to cited text no. 2
Nicolini G, Clivio A, Vanetti E, Krauss H, Fenoglietto P, Cozzi L, et al. Evaluation of an aSi-EPID with flattening filter free beams: Applicability to the GLAaS algorithm for portal dosimetry and first experience for pretreatment QA of RapidArc. Med Phys 2013;40:111719.  Back to cited text no. 3
Nicolini G, Fogliata A, Vanetti E, Clivio A, Cozzi L. GLAaS: An absolute dose calibration algorithm for an amorphous silicon portal imager. Applications to IMRT verifications. Med Phys 2006;33:2839-51.  Back to cited text no. 4
Matsumoto K, Okumura M, Asai Y, Shimomura K, Tamura M, Nishimura Y, et al. Dosimetric properties and clinical application of an a-si EPID for dynamic IMRT quality assurance. Radiol Phys Technol 2013;6:210-8.  Back to cited text no. 5
Fogliata A, Garcia R, Knoos T, Nicolini G, Clivio A, Vanetti E, et al. Definition of parameters for quality assurance of flattening filter free (FFF) photon beams in radiation therapy. Med Phys 2012;39:6455-64.  Back to cited text no. 6
Fogliata A, Clivio A, Fenoglietto P, Hrbacek J, Kloeck S, Lattuada P, et al. Quality assurance of rapidArc in clinical practice using portal dosimetry. Br J Radiol 2011;84:534-45.  Back to cited text no. 7
Min S, Choi YE, Kwak J, Cho B. Practical approach for pretreatment verification of IMRT with flattening filter-free (FFF) beams using Varian portal dosimetry. J Appl Clin Med Phys 2015;16:40-50.  Back to cited text no. 8
McDermott LN, Louwe RJ, Sonke JJ, van Herk MB, Mijnheer BJ. Dose-response and ghosting effects of an amorphous silicon electronic portal imaging device. Med Phys 2004;31:285-95.  Back to cited text no. 9
McCurdy BM, Luchka K, Pistorius S. Dosimetric investigation and portal dose image prediction using an amorphous silicon electronic portal imaging device. Med Phys 2001;28:911-24.  Back to cited text no. 10
Gustafsson H, Vial P, Kuncic Z, Baldock C, Denham JW, Greer PB, et al. Direct dose to water dosimetry for pretreatment IMRT verification using a modified EPID. Med Phys 2011;38:6257-64.  Back to cited text no. 11
Menon GV, Sloboda RS. Quality assurance measurements of a-Si EPID performance. Med Dosim 2004;29:11-7.  Back to cited text no. 12
Van Esch A, Huyskens DP, Behrens CF, Samsoe E, Sjolin M, Bjelkengren U, et al. Implementing rapidArc into clinical routine: A comprehensive program from machine QA to TPS validation and patient QA. Med Phys 2011;38:5146-66.  Back to cited text no. 13
Low DA, Harms WB, Mutic S, Purdy JA. A technique for the quantitative evaluation of dose distributions. Med Phys 1998;25:656-61.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]

  [Table 1]


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