British Journal of Radiology (2005) 78, 737-741
© 2005 British Institute of Radiology
doi: 10.1259/bjr/97956788
An assessment of clinically optimal gold marker length and diameter for pelvic radiotherapy verification using an amorphous silicon flat panel electronic portal imaging device
A M Henry, FRCR1,
J Stratford, DCR(T)1,
J Davies, DCR(T)1,
C McCarthy, BSc1,
R Swindell, MSc2,
J Sykes, MSc3,
C J Moore, PhD3,
P Price, FRCR1 and
V S Khoo, FRACR1
1 Academic Department of Radiation Oncology, University of Manchester, 2 Department of Medical Statistics and 3 Northwest Medical Physics, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK
Correspondence: Dr Ann Henry, Clinical Research Fellow, Academic Department of Radiation Oncology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK
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Abstract
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Verification of target organ position is essential for the accurate delivery of conformal radiotherapy. Megavoltage electronic portal imaging with flat panel amorphous silicon detectors delivers high quality images that can be used for verification of bony landmark position. Gold markers implanted into the target organ can be visualized and used as a surrogate of actual organ position. On-line compensation for marker displacement, by adjusting patient position, can reduce geometric errors associated with radiation delivery. This study assesses the optimal marker length and diameter to be used with an amorphous silicon (a-Si) flat panel detector and electronic portal images (EPIs), prior to implementation of a clinical programme of gold marker insertion in prostate cancer patients. Seven marker sizes varying from 3 mm to 8 mm in length and 0.8 mm to 1.1 mm in diameter were investigated in a group of patients undergoing pelvic radiotherapy using an 8 MV Elekta SL20 linear accelerator. Markers were placed on the skin entry and exit sites of the treatment beam and EPIs in both lateral and anterior pelvic views were acquired. Three observers independently assessed visibility success and failure using a subjective scoring system. Markers less than 5 mm in length or 0.9 mm in diameter were poorly visualized (<70% visualization success in lateral EPIs). The marker measuring 0.9 mm x 5 mm appears to be clinically optimal in pelvic radiotherapy patients (80% visualization success in lateral EPIs) and will be used for actual organ implantation.
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Introduction
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Prostate cancer is now the most common malignancy diagnosed in UK men with an incidence of over 24 000 new cases per year [1]. With the widespread use of prostate-specific antigen (PSA) testing and an increasingly elderly population, more individuals will be diagnosed and require intervention. A significant proportion requiring active intervention undergo radical radiotherapy and in those with intermediate or high risk disease improved outcomes may be achieved by delivering higher or escalated doses of radiation [2, 3]. Delivering escalated doses of radiation requires the use of conformal radiotherapy or intensity-modulated radiotherapy (IMRT) to maintain acceptable toxicity rates [4]. Modern treatment planning systems allow the delivery of highly complex and conformal radiation to the target volume. As treatment becomes more conformal, it is essential that internal organ motion is compensated for, so that the risk of geographic miss is reduced. The prostate can undergo significant displacement over the 4 to 7 weeks a course of fractionated external bean radiotherapy is delivered [5]. One method of compensation for both interfractional prostate motion and radiotherapy treatment set-up errors is the use of fiducial markers implanted into the prostate gland [6, 7]. The markers act as a surrogate of actual prostate position and can be visualized using electronic portal imaging devices (EPID). Prostate displacement and treatment set-up errors can be reduced using on-line imaging of implanted markers and adjustment of the patient's position if necessary. The planned patient group are men with intermediate and high risk prostate cancer who will have had a course of neoadjuvant hormone ablation prior to the commencement of radical radiotherapy. Hormone ablation causes the prostate to shrink by 20–50% [8] and may make implantation technically more difficult. We plan to insert three markers into the prostate and it is essential that the smallest possible marker is used to minimize morbidity and reduce the risk of marker overlap on EPIs. Prior to commencing a pilot study of marker implantation in prostate cancer patients, we investigated the clinically optimal marker lengths and diameters for use with an amorphous silicon flat-panel imager (iView GT; Elekta Oncology Systems, Crawley, UK).
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Methods and materials
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Seven marker sizes varying from 3 mm to 8 mm in length and 0.8 mm to 1.1 mm in diameter were investigated. The initial assessment of length used 0.8 mm diameter markers of 3 mm, 4 mm, 5 mm and 8 mm lengths, respectively. Subsequently, marker diameters of 0.9 mm, 1.0 mm and 1.1 mm were investigated (all 5 mm length). Pure gold is used as it has a high density and is therefore visible on megavoltage imaging. It is also readily available commercially. The iView GT EPID was used. This system has an amorphous silicon flat panel imager with a detection area of 41 cm x 41 cm and pixel pitch of 400 µm (1024 x 1024 pixels). The image acquisition rate is approximately 3 frames per second. All images were generated by integrating the frames acquired during the total radiation dose delivered. The number of frames integrated during beam delivery was estimated to range between 10 and 20. Cylindrical markers can be particularly difficult to clearly identify when overlying linear bony structures such as those of the femur when imaged laterally. As multiple markers will be used clinically, it is not essential to identify all markers all of the time. We estimate a visualization success rate of approximately 70–80% to be sufficient for clinical use.
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Optimal marker length
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Following informed verbal consent, a group of nine patients undergoing radiotherapy for pelvic malignancy using a four field box technique in a supine position were chosen. Patients were of similar physical size and were treated on 8 MV Elekta SL20 linear accelerators (Elekta Oncology Systems, Crawley, UK).
Two templates of 3 mm thick Perspex with dimensions of 10 cm x 10 cm were designed. Gold markers of different lengths, but a consistent diameter of 0.8 mm, were glued on randomly as follows:
Template 1 – 14 markers of 8 mm length and 14 markers of 4 mm length
Template 2 – 14 markers of 5 mm length and 14 markers of 3 mm length
On two treatment days the templates were placed on the patients' skin prior to the delivery of radiation and EPIs acquired of each of the four treatment fields. Templates were placed at the field centre in a consistent orientation. On the first day the 8 mm and 4 mm marker template was imaged, and on the second the 3 mm and 5 mm marker template. By placing the templates on either the anterior (gantry 0°) or right lateral surface (gantry 270°) of the patient, EPIs were acquired of markers on both the entrance and exit surfaces. This represents both the best and worst possible imaging scenarios for each case.
After all the images were acquired, a group of three radiographers independently scored the visibility of the markers on the EPIs. Images were viewed blind and in a random order to try and reduce any bias due to pattern recognition. A subjective scoring system was used as described in Table 1
. Poorly visible markers were quantified as those images that the radiographers would not be able to use confidently and moderately visible markers were those that could be confidently used for verification and patient repositioning.
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Optimal marker diameter
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Subsequently, following informed verbal consent, a second group of nine patients undergoing radiotherapy for pelvic malignancy using a four field box technique in a supine position were chosen. Patients were of similar physical size and were treated on 8 MV Elekta SL20 linear accelerators.
Template design was changed at this point and only one size of marker was fixed to each individual template. As previously, templates of 3 mm thick Perspex with dimensions of 10 cm x 10 cm were used. Gold markers, of 0.9 mm, 1.0 mm or 1.1 mm diameter, respectively, and all of a standard 5 mm length were glued randomly on (Figure 1) as follows:
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Figure 1. Three templates each with randomly placed 0.9 mm, 1.0 mm, and 1.1 mm diameter markers, respectively.
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Template 1 – 13 markers of 0.9 mm diameter and 5 mm length
Template 2 – 13 markers of 1.0 mm diameter and 5 mm length
Template 3 – 13 markers of 1.1 mm diameter and 5 mm length
On three sequential treatment days the templates were placed on the patients' skin prior to the delivery of radiation and EPIs acquired of each of the four treatment fields. Templates were placed at the field centre in a consistent orientation. On the first day the 0.9 mm marker template was imaged, on the second the 1.0 mm marker template and on the third the 1.1 mm marker template. By placing the templates on either the anterior (gantry 0°) or right lateral surface (gantry 270°) of the patient, EPIs were acquired of markers on both the entrance and exit surfaces, again representing both the best and worst possible imaging scenarios for each case.
After the images were acquired, a group of three radiographers independently scored the visibility of the markers on the EPIs. Images were viewed blind and in a random order to try and reduce any bias due to pattern recognition. A subjective scoring system was used as described previously.
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Results
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Scores of 0 or 1, i.e. markers not visible or poorly visible, were classified as visualization failures. Scores of 2 or 3, i.e. markers moderately or clearly visible, were classified as visualization successes. Table 2 gives a summary of the successful visualization scores as a proportion of the maximum achievable score. For marker length the maximum achievable score was 378 (27 images x 14 markers) and for diameter it was 351 (27 images x 13 markers), 338 (26 images x 13 markers) or 325 (25 images x 13 markers). Ratios were then converted into percentages for each of the seven markers in each of the fours views, namely the anteroposterior (AP) beam entry and exits and the lateral beam entry and exits. Missing scores were classed as visualization failures. All markers were seen well (>70% visualization success) in the AP views (Figure 2).
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Table 2. Successful visualization scores as a proportion and percentage for each marker size and image projection
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Figure 2. Successful visualization (%) in anterior-posterior (AP) electronic portal images (EPIs) for each of the seven marker sizes. Error bars indicate ± 2 SD. Results are from EPIs acquired with markers on either the entry or exit site of the treatment beam.
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Lateral views demonstrated that the markers measuring 3 mm x 0.8 mm, 4 mm x 0.8 mm and 5 mm x 0.8 mm were poorly visualized (<70% visualization success) and would be likely to be sub-optimal if used clinically (Figure 3). The marker measuring 0.9 mm x 5 mm combined good visibility with small size (approximately 80% visibility success).
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Figure 3. Successful visualization (%) in lateral electronic portal images (EPIs) for each of the seven marker sizes. Error bars indicate ± 2 SD. Results are from EPIs acquired with markers on either the entry or exit site of the treatment beam.
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Discussion
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This study demonstrates that gold markers measuring 0.9 mm x 5 mm should provide an optimal compromise between size and visibility on EPIs taken using an a-Si flat panel imager. The development of a-Si flat panel imagers has improved the contrast resolution of EPIs and has facilitated the use of smaller markers. Marker implantation is an invasive procedure, but the use of the smaller diameter markers makes implantation easier and reduces associated morbidity. The marker length used to assess diameter size was fixed at 5 mm. This length was chosen to facilitate implantation into smaller glands and to reduce the risk of marker overlap in EPIs. Previously published clinical studies have used this length successfully (Table 3).
Verification using EPIs in lateral pelvic images is more difficult than in AP views because of reduced contrast due to increased attenuation. This applies to both verification using bony landmarks and implanted markers. This is confirmed in this study where all markers displayed good visibility in the AP images but only the larger markers were successfully visualized in the lateral EPIs. Marker placement on entry or exit site had no significant impact on visibility.
The marker assessment was carried out by radiographers experienced in on-line verification using EPIs. This is important as we envisage verification using implanted markers to be radiographer led. The subjective scoring system used quantifies the percentage of images that radiographers would be confident to use for actual patient repositioning. Markers that are moderately or clearly visible can be accurately template matched with the reference image and should allow radiographers to make precise adjustments in three dimensions confidently where clinically appropriate.
There are few other published studies assessing optimal marker size prior to implantation. Nederveen et al assessed three different sized gold markers measuring 1.2 mm x 5 mm, 1.0 mm x 5 mm and 1.0 mm x 10 mm, respectively [9]. Markers were placed on the lateral exit skin surface and images acquired using 1–2 MU. The smallest marker (1.0 mm x 5 mm) was detected in over 90% of lateral images using an automated detection algorithm in combination with an a-Si flat panel imager. This is a higher detection rate than the visibility rate of 74% found by the observers in this study for 1.0 mm x 5 mm seeds placed on the lateral exit surface. The flat panel imager used by Nederveen et al in their work was an RID 256-L which has a pixel pitch of 800 µm. This is twice that of the iViewGT panel that is used in this study and while this means the inherent resolution of our panel is likely to be better, the signal to noise ratio will be reduced with the possibility that low contrast small objects will be harder to detect.
Sykes et al [18] developed an auto-detection algorithm and studied the detection efficiency of 0.8 mm x 5 mm seeds for seeds placed on the exit and entrance surfaces of AP images. In their study the same imaging panel was used however images were acquired with just a single frame. They reported average detection rates of 85% for unconstrained whole image searches which increases to 93% when the search is constrained to a 2 cm x 2 cm area around each seed position. These results are remarkably similar to the visibility rate of 90% for seeds in combined AP images reported in this study.
Most clinical studies in prostate cancer patients have used high purity gold markers of a variety of sizes from 3 mm to 30 mm in length and 0.8 mm to 2 mm in diameter [6, 7, 10–17]. Contrast resolution on megavoltage imaging depends on electron density. Gold has a high specific gravity and is often used as it is readily commercially available. Other dense metals such as platinum, titanium and tungsten can be used. As Table 3
demonstrates, earlier studies used portal films or camera based EPIDs, with larger markers up to 30 mm in length [10–12]. The improvement of contrast resolution with a-Si flat panel imagers has facilitated the use of smaller implanted prostate markers of the order of 1 mm x 3 mm [6, 7]. As shown in this study a reduction in the length of markers below 4 mm necessitates an increase in the diameter used. Increasing the diameter may mean using a larger needle to introduce the marker and is likely to have more impact on morbidity than increasing the length alone.
The development of improved imaging and faster template matching now opens up the possibility of imaging and correcting in real-time [6, 7]. Using technology currently available in most radiotherapy departments, the reduction of both repositioning and motion errors may be achieved by using a radiographer lead imaging protocol based on implanted markers, ensuring more precise and accurate delivery of radiotherapy to the prostate.
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Conclusions
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In this study gold markers measuring 0.9 mm x 5 mm are likely to be clinically optimal for radiotherapy verification using EPIDs and an a-Si flat panel imager in pelvic cancer patients.
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Acknowledgments
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We would like to thank medical illustration and the Consultant Clinical Oncologists at the Christie Hospital, in particular, Dr R D Hunter, Dr S E Davidson, Dr J P Logue, Dr J P Wylie, Dr R A Cowan and Dr M P Saunders who referred their patients' for the study. VSK is supported by Cancer Research UK Grant C153/A1798. AH is supported by the Christie Hospital Endowment Fund and the Wade Centre for Radiotherapy Research is funded by the Christie Hospital Centenary Fund.
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Footnotes
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Current address for Dr V S Khoo, Royal Marsden Hospital and Institute of Cancer Research, Fulham Road, London SW3 6JJ, UK. 
Received for publication March 1, 2004.
Revision received July 23, 2004.
Accepted for publication February 24, 2005.
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Abstract
Introduction
