Air kerma and absorbed dose standards for reference dosimetry in brachytherapy

This article reviews recent developments in primary standards for the calibration of brachytherapy sources, with an emphasis on the currently most common photon-emitting radionuclides. The introduction discusses the need for reference dosimetry in brachytherapy in general. The following section focuses on the three main quantities, i.e. reference air kerma rate, air kerma strength and absorbed dose rate to water, which are currently used for the specification of brachytherapy photon sources and which can be realized with primary standards from first principles. An overview of different air kerma and absorbed dose standards, which have been independently developed by various national metrology institutes over the past two decades, is given in the next two sections. Other dosimetry techniques for brachytherapy will also be discussed. The review closes with an outlook on a possible transition from air kerma to absorbed dose to water-based calibrations for brachytherapy sources in the future.Successful radiotherapy requires an accurate measurement of the radiation source output as part of a crucial quality assurance (QA) programme, as recommended by both the American Association of Physicists in Medicine (AAPM) Task Group No. 56 (TG-56)¹ and the European Society for Radiotherapy and Oncology (ESTRO).² Radioactive brachytherapy sources used for cancer treatment need to be calibrated at radiotherapy centres before clinical use. The purpose of the independent source calibration at the clinic is to verify the source strength stated on the vendor''s source calibration certificate,³ to ensure traceability to appropriate national or international standards and to make sure that dose measurements between different radiotherapy centres are consistent.² This enables clinicians to compare treatment techniques for specified radiation doses with the aim to improve the treatment outcome for cancer patients. The AAPM TG-56 report¹ recommends brachytherapy dose delivery accuracy within 5–10% with source calibration accuracy within 3%. The expanded uncertainties quoted here are based on a standard uncertainty multiplied by a coverage factor k = 2 (two standard deviations), providing a coverage probability of approximately 95%. Many components contribute to the overall uncertainty in the radiation dose delivered by brachytherapy sources and the target uncertainty of <10% (k = 2) may be difficult to achieve.⁴ The aim, however, is to keep the uncertainty in the delivered dose at the lowest possible level, which requires all dosimetric practices to be optimized. Accurate knowledge of the source strength is one of the steps in the dosimetry chain.⁵The source strength of brachytherapy sources can be measured with traceably calibrated radiation dosemeters. The calibration chain starts at the national standards laboratories, which develop and maintain primary standards for radiation qualities used in clinics. The primary standards are instruments of the highest metrological quality, which realize physical quantities from first principles.⁶ The accuracy of the primary standards is verified by comparison with similar standards of other laboratories, which are part of the international measurement system. Primary standard instruments can be very complex and too awkward to be used for routine measurements in the hospital environment. Commercially available secondary standard dosemeters, such as well-type ionization chambers,⁷ are more suitable and practical for QA measurements of brachytherapy sources in the clinic. These instruments can be traceably calibrated against a primary standard [either directly at a primary standards dosimetry laboratory (PSDL) or via a secondary standards dosimetry laboratory] and subsequently used by hospital physicists or source vendors to measure the source strength of brachytherapy sources.The brachytherapy source strength is an important input parameter for the treatment planning system (TPS), which calculates the dose distribution in tissue close to the radiation source.This review article is concerned with reference dosimetry for sealed brachytherapy photon sources that involves measuring either the air kerma rate at a reference distance of 1 m or the absorbed dose rate to water at a reference distance of 1 cm from the centre of the source. The article focuses on recent trends in the development of primary standards for three of the currently most commonly used photon-emitting brachytherapy source types, low-dose-rate (LDR) ¹²⁵I and ¹⁰³Pd seeds and high-dose-rate (HDR) ¹⁹²Ir sources. The discussion of standards for β-emitting brachytherapy sources is outside the scope of this review. Further details on primary standards for other photon-emitting and β-emitting brachytherapy sources can be found in a comprehensive review paper by Soares et al.⁸     

Current state of the art brachytherapy treatment planning dosimetry algorithms

Following literature contributions delineating the deficiencies introduced by the approximations of conventional brachytherapy dosimetry, different model-based dosimetry algorithms have been incorporated into commercial systems for ¹⁹²Ir brachytherapy treatment planning. The calculation settings of these algorithms are pre-configured according to criteria established by their developers for optimizing computation speed vs accuracy. Their clinical use is hence straightforward. A basic understanding of these algorithms and their limitations is essential, however, for commissioning; detecting differences from conventional algorithms; explaining their origin; assessing their impact; and maintaining global uniformity of clinical practice.Conventional, Task Group (TG)43-based¹ dosimetry marked an improvement over prior dose calculation formalisms for brachytherapy treatment planning by advocating the use of a source strength quantity traceable to international standards, the introduction of two-dimensional (2D) source anisotropy, and global uniformity in source characterization as well as clinical dosimetry practice. In the past decade, brachytherapy has progressed from the traditional surgical paradigm to modern three-dimensional (3D) image-based treatment planning systems (TPSs) and dose delivery. The information available through patient imaging, however, had not been fully exploited since TG43-based dosimetry relies on source-specific data pre-calculated in a standard homogeneous water geometry.^1–3 Hence, it disregards patient-specific radiation scatter conditions and the radiological differences of tissue or applicator materials from water.In response to literature on the effect of these shortcomings, which has been reviewed in several recent publications,^4–7 TPSs have become commercially available that include improved dosimetry algorithms, collectively referred to as model-based dosimetry algorithms (MBDCAs). At the time of writing, these include a deterministic solver of the linear Boltzmann transport equation (LBTE)^8–10 and a collapsed cone superposition (CCS) algorithm^11–17 for ¹⁹²Ir high-dose-rate (HDR) applications.This work reviews the basic features of these algorithms and their clinical implementation and presents illustrative results of their performance. Monte Carlo (MC) simulation is also briefly discussed since, besides being a candidate MBDCA for clinical implementation, it is used for obtaining input data for MBDCAs, as well as for their testing.     

Multistage evaluation and commissioning of a pre-calibrated, single-use OneDosePlus MOSFET system for in vivo dosimetry in a radiotherapy department

Objectives

The aim was to determine the agreement between absorbed dose measurements using the OneDosePlus and treatment planning system calculations in ideal circumstances, minimising patient-related uncertainties, before deciding upon action levels.

Methods

A OneDose metal oxide semiconductor field-effect transistor (Sicel Technologies, Morrisville, NC) in vivo dosimetry system was subjected to a multistage evaluation that tested standard and non-standard field conditions related to treatment planning system calculations for an anthropomorphic phantom.

Results

The system was found to perform within manufacturer specifications. Batch uniformity was found to be within specification when measured using a method described by Halvorsen. A modification used to assess statistical distribution of response showed an increase in the value of two standard deviations (2σ) from ±2.3 to ±2.9%, which was still within the manufacturer-stated value of ±5%. The tests using the anthropomorphic phantom also emphasised the fact that patient density inhomogeneities in the region of the D_max point will affect the dose calculated by the treatment planning system and delivered to the patient.

Conclusion

The OneDose system does not account for these inhomogeneities, leading to dependence in the deviation between expected and reported dose on inhomogeneity and choice of calculation algorithm.In the 2006 annual report [1], the Chief Medical Officer of the Department of Health recommended that in vivo dosimetry (IVD) monitoring should be used at the beginning of each course of radiotherapy treatment; this was later endorsed in the foreword of “Towards Safer Radiotherapy” [2]. IVD has the potential to detect dosimetric errors between the planned and the delivered radiotherapy treatment dose, allowing the remaining treatment fractions to be corrected [1].Following incidents in recent years, the Scottish Government has adopted this recommendation. In response to this, Ninewells Hospital''s Radiotherapy Department purchased a dosimetry system (OneDose; Sicel Technologies, Morrisville, NC). The OneDose system uses a single-use, pre-calibrated metal oxide semiconductor field-effect transistor (MOSFET) placed on the patient surface on the central axis to measure the maximum incident dose for one beam. OneDose dosemeters have no build-up cap and are designed for use with electrons and photons with added build-up material. OneDosePlus dosemeters (Sicel Technologies) have an integral build-up cap and are used only with photons with no additional build-up material. Previous evaluation tests of the OneDose MOSFET-based IVD system have only considered performance in standard field conditions on solid water phantoms for dosemeters without inherent build-up caps in the megavoltage range for photons. It is important to note the difference in calibration methods between the dosemeters with and those without build-up caps. OneDose dosemeters are calibrated to report dose to the MOSFET under full electronic equilibrium conditions, which is then source-to-surface distance (SSD) corrected to dose at depth of maximum dose. OneDosePlus dosemeters are calibrated to give dose at the depth of maximum dose directly without application of additional build-up material. The build-up cap, in conjunction with the energy correction factor, is stated by the manufacturer to allow the OneDosePlus dosemeter to be valid for use with photons between 6 MV and 18 MV.Halvorsen [3] investigated reference condition fields for OneDose dosemeters, but the study did not include an investigation of OneDosePlus dosemeters; in addition, he did not evaluate temperature dependence. Other centres have performed similar evaluations before proceeding to pilot studies on patient treatments to determine action levels (personal correspondence and submitted reports from Scottish centres in response to the Scottish Radiotherapy Advisory Group''s request for current status updates in the action notes of their meeting on 18 June 2009 [4]).This paper describes the first two stages of a three-stage implementation. The aim was to determine the agreement between absorbed dose measurements using the OneDosePlus and treatment planning system (TPS) calculations in ideal circumstances, minimising patient-related uncertainties, before deciding upon action levels. The first stage builds on the work by Halvorsen [3] and includes an investigation of angular and temperature dependence. The second stage considers the effect of non-standard field sizes and geometries, positional dependence in asymmetric fields and the effect of inhomogeneous tissue densities. The effect of the treatment planning dose calculation algorithm on the difference between measured dose and predicted dose is also explored. The third stage will be a pilot study considering practical implementation in radiotherapy. The work presented in this paper comprises the first and second stages.     

Audit of the job satisfaction levels of the UK radiography and physics workforce in UK radiotherapy centres 2012

Objective:

Workforce planning reports identify a staff shortfall that jeopardizes the ability of UK radiotherapy centres to meet future demands. Obtaining an understanding of the work experiences of radiotherapy professionals will support the development of strategies to increase job satisfaction, productivity and effectiveness.

Methods:

A quantitative survey assessed job satisfaction, attitudes to incident reporting, stress and burnout, opportunities for professional development, workload, retention and turnover. Clinical oncologists were not included, as the Royal College of Radiologists, London, UK, had recently assessed their members'' satisfaction. All questions were taken from validated instruments or adapted from the “UK National Health Service Staff Survey”.

Results:

The survey yielded 658 completed responses (approximately 16% response rate), from public and private sectors. Over a third (36%) of respondents were classified as satisfied for job satisfaction with 11% dissatisfied and the remaining 53% ambivalent. A significant proportion of clinical staff (37.5%) report high emotional exhaustion. Presenteeism was an issue with 42.4% attending work despite feeling unable to fulfil their role.

Conclusion:

Radiotherapy professionals are prone to the effects of compassion fatigue and burnout. Attention must be paid to workload and its impact on practitioners'' job satisfaction. Professional development that is supported and informed by a performance development review is a simple and effective means of enhancing satisfaction. Individuals have a responsibility to themselves and their colleagues as their behaviours and attitudes influence job satisfaction.

Advances in knowledge:

This work identifies areas for future research to enhance the professional resilience of practitioners, in order to provide high-quality treatments.An increasing incidence of cancer and an ageing population coupled with improved, expanded screening programmes and the introduction of new more-complex treatment technologies are leading to an increased demand for radiotherapy.¹ In the UK, National Radiotherapy reports have consistently identified shortfalls in key staff groups to meet this increased demand.^2–4Interest exists in providing increased flexibility for patient appointments⁵ in the UK and maximizing the use of high-cost equipment such as linear accelerators.⁶ Currently, 90% of radiotherapy is delivered between 9 am and 5 pm, Monday to Friday.⁵ The professional bodies in the UK are establishing a working party to develop guidance for services in extending the working hours and improving access for patients. A more flexible, expansive service is proposed for future working, and this is likely to require additional personnel and a flexible workforce.The combination of increased cancer incidence, drive for quality⁷ and an increasingly informed and empowered patient population has seen the projections for radiotherapy provision rise. The National Radiotherapy Advisory Group⁴ reported that a significant increase in current establishment is required, alongside retaining and developing the current workforce.^4,7 More recent estimates employing the workforce integrated planning tool,⁸ Malthus⁹ and the Radiotherapy Data Set¹⁰ quantify the requirement as a 39% increase in therapeutic radiography workforce and a 31% increase in the radiotherapy physics workforce by 2016.⁷There is a concern that the workforce is being placed under considerable pressure, and this article reports on work that has been undertaken to examine aspects of this. Maintaining a motivated radiotherapy workforce is critical to the safe delivery of high-quality radiotherapy services. Maintaining and improving morale in the existing workforce will be a key success factor in delivering high-quality treatment and care.^4,11,12 Recruitment, retention and development through improved management and influencing perceptions must remain a priority.Implementation of the career progression framework, for example, the four-tier structure for therapeutic radiographers, offers potential for greater job satisfaction by offering a professional development opportunity. In 2012, only 4 out of 50 English National Health Service (NHS) centres reported that they had implemented the career progression framework for radiography fully⁷ within radiotherapy, this may also be leading to less job opportunities and career development. There is a need to review skill requirements across the pathway in response to changing technology and demands to ensure that services are developed effectively and efficiently and to a high standard focused around the needs of patients. The size and skill mix of the radiotherapy workforce remains a potential barrier to increasing radiotherapy access for patients, developing sufficient workforce to meet the likely growth of the service is a challenge.Health Education England has recently recommended a modest increase in training commissions (3.1% for therapeutic radiographers),¹³ although the main focus must remain on reducing attrition from undergraduate training of radiographers.¹⁴ The most frequently cited rationale for not completing training is poor clinical placement experience, followed by perceived incidents of bullying and harassment in the clinical or academic environment.^15–17 If morale is low amongst the qualified workforce, this is likely to have an impact on students'' placement experience. In addition to students reporting bullying and harassment, there is evidence of bullying in the qualified workforce.^18,19 This may be a manifestation of low morale. Also, clinical sites need to be aware that making extra training capacity may negatively impact on placement opportunities for students.

Shortage of radiotherapy workforce

The most recent data report a 6.3% and 8.2% vacancy for therapeutic radiographers and clinical scientists, respectively.²⁰ The report identified a geographical variation in vacancies, and also a variation between vacancy rates for staff groups within medical physics departments in the UK. Vacancy rates are reported as 14.6% in Scotland for physics and radiography, and an average vacancy rate amongst clinical technologists, dosimetrists and engineers of >9% across the UK. Therapeutic radiographers remain on the UK shortage occupation list.²¹ The vacancy situation for the radiography workforce is exacerbated by significant attrition from therapy radiography training programmes^14–17 (average, 36.5%; 2010/11), which remains consistently higher than that of comparable professions. Unpublished data [College of Radiographers Approvals and Accreditation Board (AAB) Annual Report, 2013, personal communication] show that attrition has dropped to 25% across the UK for those starting their training in 2010 and completing it before 31 August, 2013. Therapeutic radiographers report more negative perceptions than other allied health professionals.²² The reasons for shortages of key radiotherapy staff are multifaceted and vary geographically.^23,24 This shortage negatively impacts on the ability to implement and routinely deliver advanced treatment techniques such as intensity-modulated radiotherapy (IMRT) and adaptive radiotherapy.¹¹ For example, 87% of NHS trusts cited a shortage of physicists as the main barrier to delivering IMRT for those conditions where a benefit may exist.²⁰ The availability and skill mix of radiotherapy personnel is one of the “rate limiting steps” in improving productivity and quality.¹²

Workforce engagement

Low job satisfaction is directly correlated to withdrawal behaviours, up to and including turnover.²⁵ Resignation, and to an extent employee engagement, is powered by two drivers; “push” and “pull” factors. Pull factors are the positives that a new opportunity may provide. Push factors are issues negatively impacting the satisfaction of a current situation. Interestingly, push factors are reported as more significant in the literature.²⁶ Push factors are also referred to as controlled factors as they are internal and influenced by the organization.²⁷ Examples of push factors include management practice, policies, employees'' empowerment and the notion of organizational justice.²⁸Organizational commitment is a predicative factor of employee retention, satisfaction and performance. The conceptualization of organizational commitment by Meyer and Allen²⁹ comprises three dimensions—affective, continuance and normative commitments. The affective commitment is an emotional attachment to the organization. The continuance commitment relates to the perceived costs, both financial and social, of leaving the organization. The normative commitment stems from an obligation to the organization. Positive outcomes are correlated with strengthening affective and normative commitments, where a strong affective commitment is associated with increased productivity and performance.^30,31When professionals are dissatisfied but remain in an organization, this may have negative effects on that individuals'' performance and happiness and, consequently, to the organization. These effects may exceed that of turnover, relating to reduced performance, withdrawal behaviours and barriers to development and promotion for others. Somewhat surprisingly, given the relationship between job satisfaction, performance and retention, a paucity of data exists investigating the radiotherapy workforce.Identifying and understanding the factors influencing satisfaction will aid the development of a strategy to enhance the engagement of radiotherapy professionals. Achieving this will give greater assurance that future productivity and quality in radiotherapy can be continually improved.

UK survey of job satisfaction

The objectives of the National Radiotherapy job satisfaction survey (JSS) were to:

• • obtain an understanding of the professional experiences influencing job satisfaction of the radiotherapy workforce, including radiographers, clinical scientists, technicians, engineers, assistant practitioners (APs), trainee APs (TAPs) and trainee clinical scientists. Oncologists were not surveyed, as the Royal College of Radiologists members'' satisfaction had been measured and reported on previously,^32–35 therefore it should be noted that where the term radiotherapy workforce is used, it refers to physics and radiography staff only.
• • support the development of strategies to enhance job satisfaction, productivity and effectiveness of the radiotherapy workforce.

     

Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy

The purpose of this study was to evaluate the in vivo dose–response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35±0.2 Gy) than the calculated equivalent whole-body dose (0.07±0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2±0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1±0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p = 0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p = 0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate.Quantification of chromosome aberrations in circulating lymphocytes is conventionally used to estimate the dose received by individuals accidentally exposed to ionising radiation. The observed frequency of dicentrics and centric rings is referred to a dose–response curve established in vitro, which provides the whole-body dose [1, 2]. When irradiation is heterogeneous over different parts of the body, only some lymphocytes are exposed. Because irradiated and unirradiated lymphocytes are mixed in the blood circulation, the dose received by the irradiated lymphocytes and consequently the dose delivered locally should be underestimated. Two mathematical models, Qdr and Dolphin''s deviation from the Poisson distribution, have been developed to assess the dose according to the fraction of exposed lymphocytes [3, 4]. Both models have been validated in vitro by mixing irradiated and unirradiated blood in different proportions [5]. These approaches have also been tested in vivo in accidental situations, with promising results [6, 7]. Furthermore, recent in vivo studies of cancer patients who had received 8 Gy of radiotherapy in a single fraction have shown that the derived partial-body dose obtained with both Qdr and Dolphin methods are in agreement with the doses estimated from the radiotherapy regimens [8].Cytogenetic assessment of cancer patients undergoing fractionated therapeutic irradiation would also be useful to evaluate the impact of the treatment on the yield of chromosome aberrations and on their distribution within the lymphocyte population. This could allow the evaluation of damage induced by such treatment in the patient''s circulating lymphocytes. Several studies have examined chromosome aberrations in blood samples from patients undergoing fractionated radiotherapy. These studies, which have used conventional cytogenetics, fluorescence in situ hybridisation (FISH) or both, showed a dose-dependent increase in the yields of aberrations, but with substantial interpatient variability [9–11]. The same variability in the rate of damage induced in lymphocytes during radiotherapy has been observed in other studies that used different measurements, such as premature chromosome condensation (PCC), micronuclei or γ-H2AX foci [12–14]. Explanations for these interpatient differences have suggested that damage yields after fractionated partial-body exposure do not depend only on the dose delivered locally, but may be also influenced by many other parameters, including individual variability in the response to ionising radiation, target field size or tumour localisation [9, 10, 12]. In fact, fractionated radiotherapy is a typical example of non-uniform exposure. During a session of radiotherapy, lymphocytes from the vascular pool may receive relatively small doses whereas those from the resident pool in the field may receive higher doses; both are ultimately mixed by the circulation in the following hours [15]. Furthermore, distribution of the lymphocyte pool may vary greatly within the human body; this implies that the geometry of irradiation may have a high impact on the proportion of vascular vs resident lymphocytes that may be irradiated. To measure the impact of radiotherapy treatment parameters on the aberration yields induced in peripheral lymphocytes, it is useful to study patients who have tumours in the same anatomical region. Therefore, to analyse the roles of the target field size and the dose rate relating to interpatient variability, we applied conventional cytogenetic methods to eight patients receiving fractionated radiotherapy for head and neck cancer. This anatomical region contains a high number of blood vessels and also a high number of lymph nodes. We evaluated the relation between the yield of dicentrics and centric rings measured in lymphocytes and the radiotherapy field size. We compared the dose estimate using cytogenetic methods with the physical doses obtained using calculations. Finally, we verified whether the test for deviation from Poisson distribution was able to detect the heterogeneity of the exposure after several fractions of radiotherapy.     

A dual two dimensional electronic portal imaging device transit dosimetry model based on an empirical quadratic formalism

Objective:

This study describes a two dimensional electronic portal imaging device (EPID) transit dosimetry model that can predict either: (1) in-phantom exit dose, or (2) EPID transit dose, for treatment verification.

Methods:

The model was based on a quadratic equation that relates the reduction in intensity to the equivalent path length (EPL) of the attenuator. In this study, two sets of quadratic equation coefficients were derived from calibration dose planes measured with EPID and ionization chamber in water under reference conditions. With two sets of coefficients, EPL can be calculated from either EPID or treatment planning system (TPS) dose planes. Consequently, either the in-phantom exit dose or the EPID transit dose can be predicted from the EPL. The model was tested with two open, five wedge and seven sliding window prostate and head and neck intensity-modulated radiation therapy (IMRT) fields on phantoms. Results were analysed using absolute gamma analysis (3%/3 mm).

Results:

The open fields gamma pass rates were >96.8% for all comparisons. For wedge and IMRT fields, comparisons between predicted and TPS-computed in-phantom exit dose resulted in mean gamma pass rate of 97.4% (range, 92.3–100%). As for the comparisons between predicted and measured EPID transit dose, the mean gamma pass rate was 97.5% (range, 92.6–100%).

Conclusion:

An EPID transit dosimetry model that can predict in-phantom exit dose and EPID transit dose was described and proven to be valid.

Advances in knowledge:

The described model is practical, generic and flexible to encourage widespread implementation of EPID dosimetry for the improvement of patients'' safety in radiotherapy.There is much interest in using an electronic portal imaging device (EPID) for dose measurements.^1–3 One of the major challenges with amorphous silicon (a-Si) EPID dosimetry is the presence of high Z material in the detector components that results in different response and scatter characteristics compared with a water-equivalent dosimeter.^4–6 Various EPID dosimetry models have been proposed in the literature to work around the non-water-equivalent properties of EPID. These models can be broadly categorized into non-transit and transit models. Non-transit models are based on measurements without any object in the beam and are, therefore, limited to only pre-treatment quality assurance (QA). Ideally, patient QA should also allow actual treatment verification to complete the dose verification process and to detect errors that would otherwise be missed by pre-treatment QA.⁷Transit models are desirable because they allow both pre-treatment and actual treatment verifications. Currently, there are only two commercially available EPID transit dosimetry solutions, EPIgray^® (Dosisoft, Cachan, France) and Dosimetry Check (Math Resolutions, Columbia, MD). The major drawback of EPIgray is that it only allows point comparison,^8,9 which is unreliable for modulated fields with steep dose gradient. Dosimetry Check has the advantage of offering two dimensional (2D) and three dimensional (3D) dose verification. The model deconvolves the EPID image with a scatter kernel to retrieve the incidence fluence and uses this fluence as an input into an independent dose calculation algorithm for dose computation.^10,11 An EPID transit dosimetry model using the convolution approach was also widely published by researchers at the Netherlands Cancer Institute (NKI-AVL) where the model is now in clinical use.^12–18Instead of using the convolution approach, an empirical method is more practical for the majority of clinical centres with limited resources for computationally intensive simulations or mathematical modelling. 2D transit dosimetry using an empirical method was first described by Evans et al¹⁹ and Symonds-Tayler et al²⁰ for an in-house imaging panel and later by Evans et al²¹ for a commercial scanning liquid-filled ionization chamber (SLIC) EPID. The technique used a quadratic equation established by Swindell²² and was based on a calibration method described by Morton et al²³ to derive coefficients for the conversion of EPID pixel value to equivalent path length (EPL). Although the technique was used for older model EPIDs with the purpose of designing compensators for breast irradiation, Kairn et al²⁴ proved that this method was also valid for a-Si EPID and suggested that the derived EPL matrix can be used as a form of treatment verification. Since dose, and not EPL, is the preferred metric for treatment verification, Kavuma et al^25,26 extended the model by converting the 2D EPL matrix to entrance and exit doses for comparisons with the treatment planning system (TPS). However, the model by Kavuma et al²⁵ was partially dependent on the TPS for the conversion of EPL to dose. Tissue phantom ratios and envelope and boundary profiles from the pencil beam convolution algorithm, Eclipse™ TPS (Varian^® Medical Systems, Palo Alto, CA), were used to calculate on-axis and off-axis doses. Furthermore, the model was tested only for conventional and wedge fields, and discrepancies were seen at the penumbra region.In this study, we present a 2D EPID transit dosimetry model based on the empirical quadratic calibration method,²³ but without relying on any specific TPS for the conversion of EPL to dose. Different from previous studies,^{19–21,23–25} in addition to deriving quadratic equation coefficients from EPID-measured dose planes, coefficients were also derived from ionization chamber (IC) dose planes measured in water. Therefore, in the current model, EPL can be calculated using input from both EPID as well as TPS, which is conventionally modelled based on water measurements. The EPL, which is a property of the attenuating object, provided a link to the two different dosimetry systems and allowed a two-way relationship for the:

• (1) prediction of in-phantom exit dose from EPID-measured dose planes, for comparison with TPS-planned dose. (The in-phantom exit dose in this study was defined as dose at 1.5 cm upstream from the beam exit surface of the phantom.) and
• (2) prediction of EPID transit dose from TPS-computed dose planes, for comparison with EPID measurement during treatment.

This model was systematically tested with open, wedge and intensity-modulated radiation therapy (IMRT) fields on homogeneous and heterogeneous slab phantoms. Comparisons were made using 2D absolute global gamma analysis, and results were further validated against measurements with a commercial 2D array device.     

Impact of biplane versus single-plane imaging on radiation dose,contrast load and procedural time in coronary angioplasty

Coronary angioplasties can be performed with either single-plane or biplane imaging techniques. The aim of this study was to determine whether biplane imaging, in comparison to single-plane imaging, reduces radiation dose and contrast load and shortens procedural time during (i) primary and elective coronary angioplasty procedures, (ii) angioplasty to the main vascular territories and (iii) procedures performed by operators with various levels of experience. This prospective observational study included a total of 504 primary and elective single-vessel coronary angioplasty procedures utilising either biplane or single-plane imaging. Radiographic and clinical parameters were collected from clinical reports and examination protocols. Radiation dose was measured by a dose–area–product (DAP) meter intrinsic to the angiography system. Our results showed that biplane imaging delivered a significantly greater radiation dose (181.4±121.0 Gycm²) than single-plane imaging (133.6±92.8 Gycm², p<0.0001). The difference was independent of case type (primary or elective) (p = 0.862), vascular territory (p = 0.519) and operator experience (p = 0.903). No significant difference was found in contrast load between biplane (166.8±62.9 ml) and single-plane imaging (176.8±66.0 ml) (p = 0.302). This non-significant difference was independent of case type (p = 0.551), vascular territory (p = 0.308) and operator experience (p = 0.304). Procedures performed with biplane imaging were significantly longer (55.3±27.8 min) than those with single-plane (48.9±24.2 min, p = 0.010) and, similarly, were not dependent on case type (p = 0.226), vascular territory (p = 0.642) or operator experience (p = 0.094). Biplane imaging resulted in a greater radiation dose and a longer procedural time and delivered a non-significant reduction in contrast load than single-plane imaging. These findings did not support the commonly perceived advantages of using biplane imaging in single-vessel coronary interventional procedures.The use of biplane imaging during diagnostic coronary angiography and coronary interventions has been reported to reduce the total contrast load to the patient compared with single-plane imaging [1–8]. Additionally, acquiring two simultaneous images from two orthogonal planes has been reported to be more efficient than single-plane imaging [2, 8–11]. However, there are conflicting reports as to whether the radiation dose to the patient differs between biplane and single-plane imaging during coronary studies [3, 10, 11].Biplane imaging allows two cineangiography runs to be recorded simultaneously with a single injection of contrast. With single-plane imaging, however, the same information can be acquired only by carrying out the two cineangiography runs serially with two separate injections of contrast [1, 2, 8, 10]. Biplane imaging enables the operator to visualise the target lesion in orthogonal planes simultaneously and was presumed to be more efficient than single-plane imaging, particularly in difficult procedures [1, 4, 9, 12]. Accordingly, examinations would become faster, use of fluoroscopy would be reduced, fewer cineangiography runs would be required and the average radiation dose to the patient would be comparatively lower than in the case of procedures performed with single-plane imaging. The contrast load with biplane imaging was also expected to be significantly reduced [3, 4, 11].These perceived advantages of biplane imaging have led to recommendations for its use in paediatric and adult cardiac catheter laboratories [1, 4, 5, 10, 12, 13]. A previous study comparing biplane and single-plane imaging in 1156 diagnostic coronary angiography procedures found a small, but notable, reduction in contrast load accompanied by significantly longer table times and screening times with biplane imaging, although radiation dose was not examined [14].Contrast-induced nephropathy (CIN) is a complication associated with prolonged hospitalisation and development of end-stage renal failure [15]. Patients with pre-existing renal disease, diabetes, congestive heart failure or older age are at the greatest risk in developing CIN [16–18]. These high-risk patients have a calculated incidence of CIN ranging from 10% to 30% [4, 18–20]. Pre-hydration is the primary intervention for preventing contrast nephropathy [18], but is not possible in the setting of emergency (primary) angioplasty procedures. The total contrast load during interventional procedures has been established as an independent predictor of CIN and could be effectively controlled by the operator during primary angioplasty cases [18, 21, 22]. Biplane imaging is commonly employed to minimise the contrast load, especially in patients with renal impairment and those who require primary coronary angioplasty procedures [1, 6, 7, 18, 23].Numerous studies have found that the radiation dose varies significantly according to tube angulations, particularly in the combination of steep left anterior oblique (LAO) with cranial or caudal angulations [24–27]. However, there are no published data on whether the radiation dose with biplane or single-plane imaging during coronary angioplasty differs between the three vascular territories: right coronary artery (RCA), left anterior descending (LAD) and left circumflex/intermediate (LCX). Furthermore, interventional cardiac procedures are operator dependent [28–30]. Hence, it was postulated that senior cardiologists would be more familiar with biplane equipment and thereby more able to reduce radiation dose, contrast load and procedural time than less experienced operators. To our knowledge, no studies have been published that compare the impact of biplane and single-plane imaging in coronary angioplasty procedures.The aims of this study were to determine whether biplane imaging reduces both contrast load and radiation dosage and shortens procedural time in patients undergoing primary or elective coronary angioplasty compared with single-plane imaging. We also investigated if there was a significant difference in radiation dose, contrast load and procedural time between biplane and single-plane imaging during coronary angioplasty in the three main vascular territories (RCA, LAD and LCX) and in procedures performed by operators with various levels of experience.     

Primary vaginal cancer: role of MRI in diagnosis,staging and treatment

Primary carcinoma of the vagina is rare, accounting for 1–3% of all gynaecological malignancies. MRI has an increasing role in diagnosis, staging, treatment and assessment of complications in gynaecologic malignancy. In this review, we illustrate the utility of MRI in patients with primary vaginal cancer and highlight key aspects of staging, treatment, recurrence and complications.The incidence of primary vaginal cancer increases with age, with approximately 50% of patients presenting at age greater than 70 years and 20% greater than 80 years.¹ Around 2890 patients are currently diagnosed with vaginal carcinoma in the USA each year, and almost 30% die of the disease.² The precursor for vaginal cancer, vaginal intraepithelial neoplasia (VAIN) and invasive vaginal cancer is strongly associated with human papillomavirus (HPV) infection (93%).^3,4 In situ and invasive vaginal cancer share many of the same risk factors as cervical cancer, such as tobacco use, younger age at coitarche, HPV and multiple sexual partners.^5–7 In fact, higher rates of vaginal cancer are observed in patients with a previous diagnosis of cervical cancer or cervical intraepithelial neoplasia.^7,8As is true for other gynaecologic malignancies, vaginal cancer diagnosis and staging rely primarily on clinical evaluation by the International Federation of Gynecology and Obstetrics (FIGO).⁹ Pelvic examination continues to be the most important tool for evaluating local extent of disease, but this method alone is limited in its ability to detect lymphadenopathy and the extent of tumour infiltration. Hence, FIGO encourages the use of imaging. Fluorine-18 fludeoxyglucose-positron emission tomography (¹⁸F-FDG-PET), a standard imaging tool for staging and follow-up in cervical cancer, can also be used for vaginal tumours, with improved sensitivity for nodal involvement compared to CT alone.¹⁰ In addition to staging for nodal and distant disease, CT [simulation with three dimensional (3D) conformations] is particularly useful for treatment planning and delivery of external beam radiation. MRI, with its excellent soft tissue resolution, is commonly used in gynaecologic malignancies and has been shown to be accurate in diagnosis, local staging and spread of disease in vaginal cancer.^11,12 While no formal studies are available for vaginal cancer, in cervical cancer MRI actually alters the stage in almost 30% of patients.^13–15Treatment planning in primary vaginal cancer is complex and requires a detailed understanding of the extent of disease. Because vaginal cancer is rare, treatment plans remain less well defined, often individualized and extrapolated from institutional experience and outcomes in cervical cancer.^1,16–19 There is an increasing trend towards organ preservation and treatment strategies based on combined external beam radiation and brachytherapy, often with concurrent chemotherapy,^14,20,21 surgery being reserved for those with in situ or very early-stage disease.²² Increasing utilization of MR may provide superior delineation of tumour volume, both for initial staging and follow-up, to allow for better treatment planning.²³     

A comprehensive study of the mechanical performance of gantry,EPID and the MLC assembly in Elekta linacs during gantry rotation

Objective:

In radiotherapy treatments, it is crucial to monitor the performance of linear accelerator (linac) components, including gantry, collimation system and electronic portal imaging device (EPID) during arc deliveries. In this study, a simple EPID-based measurement method is suggested in conjunction with an algorithm to investigate the stability of these systems at various gantry angles with the aim of evaluating machine-related errors in treatments.

Methods:

The EPID sag, gantry sag, changes in source-to-detector distance (SDD), EPID and collimator skewness, EPID tilt and the sag in leaf bank assembly owing to linac rotation were separately investigated by acquisition of 37 EPID images of a simple phantom with 5 ball bearings at various gantry angles. A fast and robust software package was developed for automated analysis of the image data. Nine Elekta AB (Stockholm, Sweden) linacs of different models and number of years in service were investigated.

Results:

The average EPID sag was within 2 mm for all tested linacs. Some machines showed >1-mm gantry sag. Changes in the SDD values were within 1.3 cm. EPID skewness and tilt values were <1° in all machines. The maximum sag in multileaf collimator leaf bank assemblies was around 1 mm. A meaningful correlation was found between the age of the linacs and their mechanical performance.

Conclusions and Advances in knowledge:

The method and software developed in this study provide a simple tool for effective investigation of the behaviour of Elekta linac components with gantry rotation. Such a comprehensive study has been performed for the first time on Elekta machines.Rotation of the treatment beam around the patient is one of the common features in radiotherapy. However, it is known that the gravity effect on several tons of radiation shielding, beam generation and shaping systems, and other components in the gantry head introduces deviations to the gantry rotation pattern from an ideal circle.^1–5 Gravity can also induce sagging of the beam collimation system.^3,6,7 Rotation of the gantry during treatment delivery can lead to additional multileaf collimator (MLC) errors (systematic shifts) owing to the displacement of the leaf bank assembly.^7–9 Moreover, linear accelerator (linac) rotation can affect gantry-mounted accessories such as the electronic portal imaging device (EPID), since the EPID-supporting arm is not mechanically perfect and rigidly attached. With the growing application of EPIDs in pre- and post-treatment dosimetry verification,^10–15 real-time dosimetry verification^16,17 and real-time tumour tracking for intrafraction motion management in modern radiotherapy,^18–20 it is essential to characterize and account for the mechanical system imperfections of linacs.There have been several studies in the literature on investigation of the EPID/gantry/collimator excursions during arc deliveries, which have been discussed in previous articles.^4,7,21 Our former studies were focused on using EPID-based methods for evaluation of the performance of Varian linacs (Varian^® Medical Systems, Palo Alto, CA). In this work, investigation is extended to the behaviour of components of Elekta linacs (Elekta AB, Stockholm, Sweden) at various gantry angles with some additional details. The aim of this study is to use a simple phantom design and collect the required data for investigation of: (a) gantry sag; (b) EPID sag, skewness and tilt; and (c) MLC bank assembly sag in Elekta machines at different gantry angles. Fast, accurate methods and algorithms are developed for automated data analysis and quantification of the system characteristics. Finally, based on the results acquired for several linacs, a generalized pattern (map) is derived for each of the above components with a sufficiently low level of uncertainty. Parameterizations of this map enable generic corrections to be applied during data acquisition and processing, which could be applicable to all Elekta EPIDs used for dosimetry or patient positioning.     

Proton MR spectroscopy and white matter hyperintensities in idiopathic normal pressure hydrocephalus and other dementias

The differentiation of idiopathic normal-pressure hydrocephalus (INPH) from other types of dementia is a clinical challenge. The aim of this prospective study was to evaluate the role of proton MR spectroscopy (MRS) and white matter hyperintensities (WMH) in the diagnosis of INPH, predicting response to therapy and differentiating INPH from other dementias. The study included 18 patients with INPH (Group 1), 11 patients with other types of dementia (Group 2) and 20 control patients (Group 3). The value of WMH scores and MRS findings in diagnosis, evaluation of response to therapy and in the differentiation of INPH from other dementias was statistically evaluated. The level of statistical significance was set at p<0.05 (Kruskal–Wallis and Mann–Whitney U-test). In both Groups 1 and 2, N-acetylaspartate (NAA)/choline-NAA/creatine ratios were significantly less than in the control group (p<0.05). The WMH and MRS findings of Groups 1 and 2 demonstrated no statistically significant correlation (p>0.05). No correlation was found between the outcome of shunt operations and WMH and MRS findings (p>0.05). In conclusion, neither WMH nor MRS were useful in differentiating INPH from other types of dementia. WMH and MRS showed no additional benefit in identifying INPH patients who will better respond to shunt therapy.Idiopathic normal-pressure hydrocephalus (INPH) is a rare disease affecting the elderly [1]. The exact aetiology of the disease is unknown and the most common symptoms are dementia, gait apraxia and urinary incontinence [1, 2]. INPH differs from other dementias in that the symptoms can show regression with cerebrospinal fluid (CSF) diversion [2, 3]. This opportunity for treatment makes it important to differentiate INPH from other dementias that cause senile changes, vascular disease and Alzheimer''s [3, 4].Many tests have been employed in the diagnosis of INPH, including CSF pressure measurements, intrathecal saline infusion tests, intermittent CSF drainage, cerebral blood flow (CBF) measurements and brain biopsy [3]. In addition, imaging methods such as radionuclide cisternography, CT, MRI, CT cisternography, phase-contrast cine MRI and perfusion MRI have also been used [5–7]. Treatment options for INPH include third ventriculostomy, ventriculoperitoneal shunt (VPS) or lumboperitoneal shunt procedures [8]. The success rate of shunt therapies varies between 30% and 65% [9–12].Some reports have emphasised that subcortical and deep white matter hyperintensities (WMH) on T₂ weighted images are more common in patients with INPH [2, 11]. This finding is attributed to ischaemia of small vessels owing to low CBF [2, 13]. Also, recent studies have reported a relationship between WMH and vascular compliance and pulsation defects [14]. Some authors suggest that the response to shunt therapy is worse in patients with WMH, while others propose the opposite [2, 7, 11, 15].Proton MR spectroscopy (MRS) is a non-invasive technique that images some of the metabolites in brain tissue [16, 17]. Although MRS is commonly used in differentiating a variety of brain lesions, the number of articles evaluating its efficacy in the diagnosis of INPH is limited [10, 18–21]. MRS can aid in analysing the severity of neuronal injury before the treatment and effects of shunt therapy [21]. N-acetylaspartate (NAA) is a metabolite mainly found in neurons and is accepted as the neuronal marker [4, 16, 17]. A decrease in NAA levels shows neuronal injury and loss, as the regeneration capacity of the neurons is limited [18, 20]. In the other dementia syndromes, the NAA peak decreases irreversibly [18–21]. By contrast, in INPH, although cerebral functions can deteriorate because of ventriculomegaly, minimal NAA decrease or neuronal loss is observed [21]. This finding implies that cerebral injury is reversible.The aim of this study was to evaluate both the efficacy of MRS and the quantification of WMH in the differential diagnosis of INPH from other causes of dementia. We also hoped to assess the ability of these approaches to predict response to therapy.     

Personal dosimetry for interventional operators: when and how should monitoring be done?

Objective

Assessment of the potential doses to the hands and eyes for interventional radiologists and cardiologists can be difficult. A review of studies of doses to interventional operators reported in the literature has been undertaken.

Methods

Distributions for staff dose to relevant parts of the body per unit dose–area product and for doses per procedure in cardiology have been analysed and mean, median and quartile values derived. The possibility of using these data to provide guidance for estimation of likely dose levels is considered.

Results

Dose indicator values that could be used to predict orders of magnitude of doses to the eye, thyroid and hands from interventional operator workloads have been derived, based on the third quartile values, from the distributions of dose results analysed.

Conclusion

Dose estimates made in this way could be employed in risk assessments when reviewing protection and monitoring requirements. Data on the protection provided by different shielding and technique factors have also been reviewed to provide information for risk assessments. Recommendations on the positions in which dosemeters are worn should also be included in risk assessments, as dose measurements from suboptimal dosemeter use can be misleading.Interventional radiologists and cardiologists have the highest exposure to radiation of any staff working with medical X-ray techniques [1,2]. The continual improvements in technology and methodology enable more challenging clinical problems to be tackled, so the numbers of procedures being performed continues to rise [3]. Because of the potential for doses received by interventional operators to be high, it is important that they are monitored effectively. Doses to the trunk are recorded routinely, but it is often not easy to decide when it is appropriate to monitor other parts of the body that are more difficult to protect and have their own dose limits [2]. The tissues that may be exposed to higher doses are the head, particularly the eyes and thyroid, the hands and the legs. The eyes have their own dose limit of 150 mSv for a classified worker, and lens opacities have been reported among interventional radiology operators that are thought to be due to X-ray exposure [4,5]. The thyroid is known to be radiosensitive and makes a significant contribution to the effective dose (E) if it is not shielded [6-9]. The skin has a dose limit of 500 mSv, which is applied to the dose averaged over 1 cm². Exposure of the hands is a matter of concern because of the need for the operator to be close to the X-ray field to carry out manipulations, and the possibility of higher doses from poor practice if the hands are exposed to the primary beam. The skin dose limit also applies to the legs and these need to be considered as they are usually closer to the region of scatter from the unattenuated X-ray beam with undercouch X-ray tubes [10].Analysis of results from extremity monitoring for medical applications reported by seven European countries has shown that hand doses from routine monitoring are lower than those reported in dedicated studies published in the literature [11]. Several factors probably contribute to this difference. The most exposed workers may not be monitored, dosemeters may not be worn on the most exposed part of the hand and use of dosemeters may be erratic. A more systematic, evidence-based approach to dose monitoring would be beneficial in trying to alleviate these problems. It is impractical to monitor doses to all sites for every interventional operator. Practices should be reviewed in risk assessments to determine appropriate dosimetry arrangements, but before any dose measurements are carried out, the information available on potential doses is limited. Measurements of the distribution of air kerma made with ionisation chambers during simulated interventional procedures can be useful for establishing where dose rates are higher [2^,8^,10^,12-15] and are helpful in assessing where staff should stand, but the information they provide relating to doses to different parts of the body, especially the hands, is limited. Many studies of the doses received by interventional operators have been carried out and information gained from these could be used in evaluating likely dose levels for application in risk assessments to establish the dose monitoring that should be undertaken.     

Diffusion-weighted MRI in the follow-up of chronic periaortitis

Objective:

To evaluate the usefulness of diffusion-weighted MRI (DWI) for the assessment of the intraindividual follow-up in patients with chronic periaortitis (CP) under medication.

Methods:

MRI data of 21 consecutive patients with newly diagnosed untreated disease were retrospectively examined before and after medical therapy, with a median follow-up of 16 weeks. DWI parameters [b800 signal, apparent diffusion coefficient (ADC) values] of the CP and psoas muscle were analysed together with the extent and contrast enhancement. Pre- and post-treatment laboratory inflammation markers were acquired parallel to each MR examination.

Results:

Statistically significant lower b800 signal intensities (p ≤ 0.0001) and higher ADC values (p ≤ 0.0001) were observed after medical treatment within the fibrous periaortic tissue. Extent and contrast enhancement of the CP showed also a statistically significant decrease (p ≤ 0.0001) in the follow-up examinations, while the control parameters within the psoas muscle showed no differences.

Conclusion:

DWI seems to be a useful method for the evaluation of response to treatment without contrast agents. The technique may be helpful in the assessment of disease activity to guide further therapeutic strategies.

Advances in knowledge:

DWI detects significant differences in the intraindividual follow-up of CP under medical therapy.Chronic periaortitis (CP) is a proliferating fibroinflammatory disease of the perivascular retroperitoneal space and aortic wall.^1–4 Owing to adventitial inflammation, some recent theories consider CP as a large vessel vasculitis.⁵ Clinical manifestations of CP include idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm and perianeurysmal retroperitoneal fibrosis.^2,6,7 The three manifestations with very similar histopathological characteristics are distinguished by the diameter of the abdominal aorta and concomitant ureteral affection.^1,3,7Specific clinical symptoms are caused by extrinsic compression of the ureters or retroperitoneal veins, resulting in hydronephrosis, oliguria, lower extremity oedema and deep vein thrombosis.^1,8Under medical treatment with steroids, CP has a good prognosis.⁷ Today tamoxifen is suggested as a safe and effective therapeutic alternative, and immunosuppressive drugs can be considered in patients with suboptimal responses to these drugs or multiple relapses.^9–11CT and MRI are the modalities of first choice for diagnosis and follow-up of CP.^1,7,12 The fibrotic para-aortic tissue shows significant contrast uptake in gadolinium-enhanced MRI.^12–14 Dynamic contrast-enhanced MRI was suggested for the assessment of the disease activity.^15,16 However, in cases with impaired renal function (e.g. by ureteral compression), gadolinium-independent imaging methods should be preferred owing to the potential development of a nephrogenic systemic fibrosis.¹⁷Diffusion-weighted MRI (DWI) is a non-contrast MR modality that has been successfully applied for the assessment of retroperitoneal masses, inflammatory abdominal aortic aneurysms and for the differentiation between retroperitoneal fibrosis and malignant retroperitoneal neoplasms.^18–21DWI indicates restricted diffusion of water, for example caused by a high cellularity in malignant disease or active inflammation. The apparent diffusion coefficient (ADC) is a quantitative parameter for the level of restricted diffusion, which is calculated from the signals of different diffusion gradients (b-values).²²In the context of untreated CP diffusion-weighted MRI may detect restricted inflammation as a sign of high cellularity caused by active inflammation.There are no data for the evaluation of intraindividual follow-up and the response to treatment by DWI of CP so far. Therefore, the aim of the present study was to analyse differences in DWI signals during follow-up in patients with CP before and after treatment. In addition, we sought to elucidate the potential of DWI in the therapy monitoring of CP.     

Iron overload: accuracy of in-phase and out-of-phase MRI as a quick method to evaluate liver iron load in haematological malignancies and chronic liver disease

Objectives

The purpose of this prospective study was to evaluate the accuracy of in-phase and out-of-phase imaging to assess hepatic iron concentration in patients with haematological malignancies and chronic liver disease.

Methods

MRI-based hepatic iron concentration (M-HIC, μmol g^–1) was used as a reference standard. 42 patients suspected of having iron overload and 12 control subjects underwent 1.5 T in- and out-of-phase and M-HIC liver imaging. Two methods, semi-quantitative visual grading made by two independent readers and quantitative relative signal intensity (rSI) grading from the signal intensity differences of in-phase and out-of-phase images, were used. Statistical analyses were performed using the Spearman and Kruskal–Wallis tests, receiver operator curves and κ coefficients.

Results

The correlations between M-HIC and visual gradings of Reader 1 (r=0.9534, p<0.0001) and Reader 2 (r=0.9456, p<0.0001) were higher than the correlations of the rSI method (r=0.7719, p<0.0001). There was excellent agreement between the readers (weighted κ=0.9619). Both visual grading and rSI were similar in detecting liver iron overload: rSI had 84.85% sensitivity and 100% specificity; visual grading had 85% sensitivity and 100% specificity. The differences between the grades of visual grading were significant (p<0.0001) and the method was able to distinguish different degrees of iron overload at the threshold of 151 μmol g^–1 with 100% positive predictive value and negative predictive value.

Conclusion

Detection and grading of liver iron can be performed reliably with in-phase and out-of-phase imaging. Liver fat is a potential pitfall, which limits the use of rSI.Iron overload is a clinically recognised condition with variety of aetiologies and clinical manifestations [1-4]. Liver iron concentration correlates closely with the total body iron stores [5]. The excess iron accumulates mainly in the liver and the progressive accumulation of toxic iron can lead to organ failure if untreated [2,4]. Several diseases causing iron overload, such as transfusion-dependent anaemia, haematological malignancies, thalassaemia, haemochromatosis and chronic liver disease, result in a large number of patients with a potentially treatable iron overload [1,2,4].Several quantitative MRI methods for iron overload measurement by multiple sequences have been established, such as proportional signal intensity (SI) methods and proton transverse relaxation rates (R₂, R₂*) [4,6,7]. A gradient echo liver-to-muscle SI-based algorithm [8] has been widely validated and used for quantitative liver iron measurement [8-11]. MRI-based hepatic iron concentration (M-HIC, μmol g^–1 liver dry weight) with corresponding R₂* [9] can be calculated with this method which is a directly proportional linear iron indicator, virtually independent of the fat fraction, as the echo times are taken in-phase [8,9]. This method showed a high accuracy in calibrations with the biochemical analysis of liver biopsies (3–375 μmol g^–1) of 174 patients. The mean difference of 0.8 μmol g^–1 (95% confidence interval of –6.3 to 7.9) between this method and the biochemical analysis is quite similar [8] to the intra-individual variability found in histological samples [12].The quantitative MRI methods are based on progressive SI decay, with the longer echo times due to relaxing properties of iron. Interestingly, this iron-induced effect is seen in MR images with multiple echoes [4,6-11], but also in dual-echo images, namely in-phase and out-of-phase imaging [13,14]. In-phase and out-of-phase imaging has become a routine part of liver MRI, performed initially for liver fat detection [6,13,15]. Quite recently some investigators have noticed an alternative approach of the sequence to detect liver iron overload due to the more pronounced SI decrease on in-phase images with the longer echo time [13,14]. Yet, to our knowledge, this is the first prospective study evaluating the accuracy of in-phase and out-of-phase imaging to assess hepatic iron concentration.The purpose of the study was to evaluate the capability and accuracy of dual-echo in-phase and out-of-phase imaging to assess hepatic iron concentration at 1.5 T in patients with haematological malignancies and chronic liver disease. MRI-based hepatic iron concentration (M-HIC, μmol g^–1) was used as a reference standard [8,9].     

Hepatic radiofrequency ablation: in vivo and ex vivo comparisons of 15-gauge (G) and 17-G internally cooled electrodes

Objective:

To compare the performance of the 15-G internally cooled electrode with that of the conventional 17-G internally cooled electrode.

Methods:

A total of 40 (20 for each electrode) and 20 ablation zones (10 for each electrode) were made in extracted bovine livers and in in vivo porcine livers, respectively. Technical parameters, three dimensions [long-axis diameter (Dl), vertical-axis diameter (Dv) and short-axis diameter (Ds)], volume and the circularity (Ds/Dl) of the ablation zone were compared.

Results:

The total delivered energy was higher in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (8.78 ± 1.06 vs 7.70 ± 0.98 kcal, p = 0.033; 11.20 ± 1.13 vs 8.49 ± 0.35 kcal, p = 0.001, respectively). The three dimensions of the ablation zone had a tendency to be larger in the 15-G group than in the 17-G group in both studies. The ablation volume was larger in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (29.61 ± 7.10 vs 23.86 ± 3.82 cm³, p = 0.015; 10.26 ± 2.28 vs 7.79 ± 1.68 cm³, p = 0.028, respectively). The circularity of ablation zone was not significantly different in both the studies.

Conclusion:

The size of ablation zone was larger in the 15-G internally cooled electrode than in the 17-G electrode in both ex vivo and in vivo studies.

Advances in knowledge:

Radiofrequency ablation of hepatic tumours using 15-G electrode is useful to create larger ablation zones.Radiofrequency ablation (RFA) is the most widely used local ablation technique for the management of primary and metastatic liver tumours. However, previous studies have reported that RFA showed a relatively higher local tumour progression rate than did hepatic resection.^1,2 One of the most important factors affecting local tumour progression was insufficient tumour-free ablation margin of hepatic parenchyma around the tumour margin.^3–6Several strategies have been developed to obtain sufficient ablation margin. In the aspect of RFA techniques, overlapping technique and combined treatment with transcatheter arterial chemoembolization can be used.^7–9 Another strategy is to use switching monopolar, bipolar or multipolar modes to deliver radiofrequency (RF) energy more efficiently.^10,11 Sufficient ablation margin can also be achieved by more efficient electrodes: internally cooled electrode increases the size of ablation zone by preventing charring around the electrode tip.^12,13 Perfusion electrodes can also enlarge the ablation zone by increasing electrical conductance and thermal conductivity.^14–16The diameter of an electrode is also known to be associated with the size of the ablation zone. Theoretically, as the diameter of an electrode becomes larger, the contact surface of the electrode with the surrounding tissue becomes bigger, thereby increasing the active electric field.^17,18 As a result, an electrode with a larger diameter is likely to create a larger ablation zone. In a previous study, Goldberg et al¹⁷ reported that the extent of coagulation necrosis by RFA increases as the diameter of an electrode increases through an in vivo experimental study. However, this study was performed with an electrode without an internal cooling system. Recently, a clinical study comparing therapeutic efficacy and safety between 15-G and 17-G internally cooled electrodes of RFA for hepatocellular carcinoma was published.¹⁹ According to that study, the 15-G internally cooled electrode created a larger ablation volume than did the 17-G electrode. However, the study was limited by selection bias owing to the retrospective study design. In addition, the ablation protocol was not exactly the same between the two groups. Therefore, the issue whether an internally cooled electrode with a larger diameter creates a larger ablation volume should be verified with ex vivo and in vivo experimental studies.The purpose of this experimental study was to compare the performance of the 15-G internally cooled RF electrode with that of the conventional 17-G electrode in both ex vivo and in vivo studies.     

Diagnostic quality of 50 and 100 μm computed radiography compared with screen-film mammography in operative breast specimens

Objective

To compare reader ratings of the clinical diagnostic quality of 50 and 100 μm computed radiography (CR) systems with screen–film mammography (SFM) in operative specimens.

Methods

Mammograms of 57 fresh operative breast specimens were analysed by 10 readers. Exposures were made with identical position and compression with three mammographic systems (Fuji 100CR, 50CR and SFM). Images were anonymised and readers blinded to the CR system used. A five-point comparative scoring system (−2 to +2) was used to assess seven quality criteria and overall diagnostic value. Statistical analysis was subsequently performed of reader ratings (n=16 925).

Results

For most quality criteria, both CR systems were rated as equivalent to or better than SFM. The CR systems were significantly better at demonstrating skin edge and background tissue (p<1×10⁻⁵). Microcalcification was best demonstrated on the CR50 system (p<1×10⁻⁵). The overall diagnostic value of both CR systems was rated as being as good as or better than SFM (p<1×10⁻⁵).

Conclusion

In this clinical setting, the overall diagnostic performance of both CR systems was as good as or better than SFM, with the CR50 system performing better than the CR100.There are currently three technologies widely available for diagnostic mammography: screen–film mammography (SFM) and two forms of large-field digital mammography [1]. The use of the term full-field digital mammography (FFDM) varies in the published literature and has been applied to both computed radiography (CR) and direct digital radiography (DR). Small-field digital mammography (SFDM) is mainly used for imaging during stereotactic biopsy [2].The advantages of digital mammography over SFM include: improved sensitivity in dense breast tissue, reduced radiation dose, the ability to manipulate images for review, and digital storage and retrieval methods [3]. CR was the earliest digital system in use. Imaging cassettes contain a re-useable photostimulable phosphor, replacing the traditional screen–film cassettes, and are then transferred to a laser reader. DR has an in-built detector and reader. Digital mammography has a lower spatial resolution than SFM, but has a very high contrast resolution. This allows the overall resolution of digital mammography to be at least equivalent to SFM [4-8], even when viewing calcification smaller than the pixel size [9]. Some CR systems have not met the quality standards of a number of governing bodies for mammography, including the European Network of Reference Assessment Centres (EUREF) and the NHS Breast Screening Programme (NHSBSP) [10,11]. This is related to the resolution achievable with 100 µm cassettes [12]. It is now known that CR systems using 50 µm cassettes can provide improved resolution, at an acceptable mean glandular dose, and have been approved for screening by the NHSBSP [13-15].Phantom studies indicate that the resolution and performance of DR are greater than those of CR [16,17], but have limitations. Although there are many clinical studies comparing the performance of DR and SFM [4-7,9,18-26], there are fewer that compare CR with SFM or DR [8,25,27-32]. We sought a method to compare the clinical diagnostic quality of two types of CR technology with that of SFM. We chose to study surgical specimens of breast tissue, which, although not absolutely comparable to in vivo mammography, allows realistic testing of image quality. In addition, multiple exposures can be obtained in reproducible conditions without irradiating the patient.     

Towards clinical assessment of velopharyngeal closure using MRI: evaluation of real-time MRI sequences at 1.5 and 3 T

Objective

The objective of this study was to demonstrate soft palate MRI at 1.5 and 3 T with high temporal resolution on clinical scanners.

Methods

Six volunteers were imaged while speaking, using both four real-time steady-state free-precession (SSFP) sequences at 3 T and four balanced SSFP (bSSFP) at 1.5 T. Temporal resolution was 9–20 frames s⁻¹ (fps), spatial resolution 1.6×1.6×10.0–2.7×2.7×10.0 mm³. Simultaneous audio was recorded. Signal-to-noise ratio (SNR), palate thickness and image quality score (1–4, non-diagnostic–excellent) were evaluated.

Results

SNR was higher at 3 T than 1.5 T in the relaxed palate (nasal breathing position) and reduced in the elevated palate at 3 T, but not 1.5 T. Image quality was not significantly different between field strengths or sequences (p=NS). At 3 T, 40% acquisitions scored 2 and 56% scored 3. Most 1.5 T acquisitions scored 1 (19%) or 4 (46%). Image quality was more dependent on subject or field than sequence. SNR in static images was highest with 1.9×1.9×10.0 mm³ resolution (10 fps) and measured palate thickness was similar (p=NS) to that at the highest resolution (1.6×1.6×10.0 mm³). SNR in intensity–time plots through the soft palate was highest with 2.7×2.7×10.0 mm³ resolution (20 fps).

Conclusions

At 3 T, SSFP images are of a reliable quality, but 1.5 T bSSFP images are often better. For geometric measurements, temporal should be traded for spatial resolution (1.9×1.9×10.0 mm³, 10 fps). For assessment of motion, temporal should be prioritised over spatial resolution (2.7×2.7×10.0 mm³, 20 fps).

Advances in knowledge

Diagnostic quality real-time soft palate MRI is possible using clinical scanners and optimised protocols have been developed. 3 T SSFP imaging is reliable, but 1.5 T bSSFP often produces better images.Approximately 450 babies born in the UK every year have an orofacial cleft [1], the majority of which include the palate [2]. While a cleft palate is commonly repaired surgically at around 6 months [3], residual velopharyngeal insufficiencies require follow-up surgery in 15–50% of cases [4]. This residual defect results in an incomplete closure of the velopharyngeal port, which in turns leads to hypernasal speech. Assessment of velopharyngeal closure in speech therapy is commonly performed using X-ray videofluoroscopy or nasendoscopy [5,6]. While nasendoscopy is only minimally invasive, it may be uncomfortable and provides only an en face view of the velopharyngeal port. In contrast, X-ray videofluoroscopy is non-invasive and produces an image which is a projection of the target anatomy. Additional information may be obtained from projections at multiple angles [5,7], but anatomical structures may overlie each other. Furthermore, soft tissue contrast, such as that from the soft palate, is poor, although it may be improved using a barium contrast agent coating [8] at the expense of making the procedure more invasive and unpleasant. Arguably the greatest drawback of X-ray videofluoroscopy is the associated ionising radiation dose, which carries increased risk in paediatric patients [9].An increasing number of research studies have used MRI to image the soft palate [10-13] and upper vocal tract [14-17]. In contrast to X-ray videofluoroscopy and nasendoscopy, MRI provides tomographic images in any plane with flexible tissue contrast. As a result, MRI has been used to obtain images of the musculature of the palate at rest and during sustained phonation [10,18,19]. It has also been used to image the whole vocal tract at rest or during sustained phonation [20-27] and with a single mid-sagittal image dynamically during speech [13,15-17,28-35].For assessment of velopharyngeal closure, dynamic imaging with sufficient temporal resolution and simultaneous audio recording is required. Audio recording during imaging is complicated by the loud noise of the MRI scanner, and both the safety risk and image degradation caused by using an electronic microphone within the magnet. As a result, optical fibre-based equipment with noise cancellation algorithms must be used [36].In order to fully resolve soft palate motion, Narayanan et al [30] suggested that a minimum temporal resolution of 20 frames s⁻¹ (fps) is required. A similar conclusion was reached by Bae et al [13], based on measurements of soft palate motion extracted from X-ray videofluoroscopy. Using segmented MRI, Inoue et al [35] demonstrated that changes in the velar position that were evident at acquired frame rates of 33 fps were not observed at 8 fps. However, MRI is traditionally seen as a slow imaging modality and achieving sufficient temporal resolution at an acceptable spatial resolution is challenging. Furthermore, as the soft palate is bordered on both sides by air, the associated changes in magnetic susceptibility at the interfaces make images prone to related artefacts.Dynamic MRI of the vocal tract has been performed using both segmented [17,33,37] and real-time acquisitions [13,15,16,28,31,38]. Segmented acquisitions [39] acquire only a fraction of the k-space data required for each image during one repetition of the test phrase and, hence, require multiple identical repetitions. While these segmented techniques permit high temporal and spatial resolutions [35], they require reproducible production of the same phrase up to 256 times [34], leading to subject fatigue. Differences between repeats of up to 95 ms in the onset of speech following a trigger have also been demonstrated [36].In contrast to segmented techniques, real-time dynamic methods permit imaging of natural speech, but require extremely rapid acquisition and often advanced reconstruction methods. The turbo spin echo (TSE) zoom technique [40] has been used to perform real-time MRI of the vocal tract [29,31] and is available as a clinical tool. The zoom technique excites a reduced field of view in the phase encode direction, hence allowing a smaller acquisition matrix and shorter scan for a constant spatial resolution. While such spin echo-based techniques are less susceptible to magnetic field inhomogeneity related signal dropout artefacts than other sequences, the frame rates achieved with these sequences are limited to 6 fps [31]. Gradient echo-based techniques have also been used to achieve similar temporal resolution [12,41,42] in the upper vocal tract, but are often used at much higher frame rates in other MRI applications such as cardiac imaging [43,44]. A number of gradient echo sequence variants exist. Fast low-angle shot (FLASH) type sequences [45] spoil any remaining transverse magnetisation at the end of every sequence repetition (TR). In contrast, steady-state free-precession (SSFP) sequences are not spoiled [46] and the remaining transverse magnetisation is used in the next TR to improve the signal-to-noise ratio (SNR), but renders the images sensitive to signal loss in the presence of motion. Balanced SSFP (bSSFP) sequences include additional gradients to bring the transverse magnetisation completely back into phase at the end of every TR [47,48]. The result is that bSSFP sequences have high SNR and are less sensitive to motion than SSFP sequences, but are more sensitive to field inhomogeneities, which cause bands of signal dropout.Both TSE and the gradient echo techniques discussed here sample in a rectilinear or Cartesian fashion, where one line of k-space is sampled in each echo. However, for real-time speech imaging, the highest acquired frame rates have been achieved by sampling k-space along a spiral trajectory [15,16,30,49]. While spiral imaging is an efficient way to sample k-space and is motion-resilient, it is prone to artefacts, particularly blurring caused by magnetic field inhomogeneities and off-resonance protons (i.e. fat) [50]. Recently, one group successfully used spiral imaging with multiple saturation bands and an alternating echo time (TE) to achieve an acquired real-time frame rate of 22 fps [13,16]. The saturation bands were used to allow a small field of view to be imaged without aliasing artefacts. The alternating TE was used to generate dynamic field maps which were incorporated into the reconstruction to compensate for magnetic field inhomogeneities. However, such advanced acquisition and reconstruction techniques are only available in a small number of research centres.The aim of this work is to optimise and demonstrate high-temporal-resolution real-time sequences available on routine clinical MRI scanners for assessment of soft palate motion and velopharyngeal closure. Consequently, radial and spiral acquisitions were excluded and the work focuses on Cartesian gradient echo sequences with parallel imaging techniques. As more clinical MRI departments now have 3 T scanners, imaging was performed at both 1.5 and 3 T to enable comparisons. At each field strength, we optimised sequences and implemented four combinations of spatial and temporal resolution in six subjects with simultaneous audio recordings.