Methods and Techniques for Comprehensive 3D Dosimetrypeople.duke.edu/~oldha009/My Papers/2014AMP_Ch05.pdf · 5.2 Methods of 3D Dosimetry The term 3D dosimetry is commonly used, but

CHAPTER 5

69

Methods and Techniques forComprehensive 3D Dosimetry

Mark Oldham, Ph.D.Professor, Department of Radiation Oncology

Duke University Medical CenterDurham, NC

5.1 Introduction..........................................................................................................70

5.2 Methods of 3D Dosimetry......................................................................................715.2.1 Materials..................................................................................................715.2.2 Dose Readout...........................................................................................75

5.3 Applications of 3D Dosimetry ................................................................................78

5.4 Summary and Recent Developments ......................................................................80

5.5 Acknowledgments.................................................................................................81

5.6 References............................................................................................................81

OLDHAM.fm Page 69 Monday, June 2, 2014 9:40 AM

ADVANCES IN MEDICAL PHYSICS – 201470

5.1 Introduction

Radiation therapy is a principle treatment modality for manycancers and other diseases. Over half of all patients diagnosedwith cancer will receive some form of radiation therapy aspart of their treatment (National Cancer Institute 2014). In thelast 15 years, the sophistication and capabilities of these treat-ments has increased dramatically. Two engines of innovationin particular can be discerned:

• the discovery and development of mathematical toolsto optimize the radiation fluence for a desired dose pre-scription and normal tissue tolerance (Webb 1989;Bortfeld et al. 1994), and

• the associated computer control and electro-mechani-cal hardware developments needed to implement thedelivery of such precise intensity-modulated radiationtreatments (IMRT) (Convery and Rosenbloom 1992;Stein et al. 1994).

An example of a modern IMRT treatment for head-and-neck cancer is shown in Figure 5–1. The figure illustrates theextraordinary potential of IMRT to deliver complex three-dimensional (3D) distributions of dose that conform to evenirregularly shaped lesions in the patient.

There are many assumptions in the mathematical model-ing leading to the virtual computer representation of apatient’s dose distribution, such as the one illustrated in Fig-ure 5–1. The limitations of the models for energy depositionand the potential for errors in radiation therapy delivery haverecently received significant attention (Ibbott 2010; Moran etal. 2011). In 2010, partly in response to several catastrophicevents (Bogdanich 2010, 2010b), the United States Congressheld hearings on the topic of how to improve safety in radia-

tion therapy (Herman 2011). Independently, the RadiologicalPhysics Center (RPC) reported unacceptably high failure ratesfor dosimetry credentialing in national clinical trials for sev-eral IMRT treatment sites: 22% and 32% for neck and spine,respectively (Ibbott 2010). These failures were detected byexamining the patterns of dose delivered to a pair of orthogo-nal 2D film planes

The concerns outlined above have led many to recognizean urgent need to radically strengthen the foundations of qual-ity assurance (QA) in radiation therapy (RT). There are, ofcourse, many aspects to a comprehensive QA program(Moran et al. 2011 and 2011b). A foundational stone, how-ever, is a comprehensive end-to-end verification of the deliv-ered dose in phantoms, normally performed during extensivecommissioning measurements when the accuracy of a newtechnique is established prior to its implementation in theclinic. Historically, in the absence of viable 3D dosimetry sys-tems, such measurements have typically been made atselected planes and points, utilizing film, thermoluminescentdosimeters (TLD), diodes, and ion chambers (Ibbott 2010).These sparse sampling methods can catch planning and deliv-ery errors, but there remains the possibility of an undetectedfailure in regions that were not measured. In this chapter wefocus on a review of the development and current state-of-the-art of a suite of 3D dosimetry techniques that can provide amore comprehensive solution to the problem of verification ofcomplex radiation therapy treatments, and 3D dose measure-ment in general. Also of interest (although not discussed fur-ther here) are in vivo methods of transit dosimetry (Mans et al.2010; Mijnheer et al. 2013) which attempt to reconstruct theactual delivered dose during a radiotherapy treatment from thefluence patterns that exit the patient, captured by a flat panel

Figure 5–1. A modern, precise radiation therapy treatment plan of the head and neck. The tailored scalloping of isodose linesaround multiple targets (prescribed dose of 66.5 Gy and 54.3 Gy, respectively) and conformal avoidance of the spinal cord andparotid glands only became achievable with the advent of intensity-modulated therapy techniques. a) transverse section. b) coro-nal section. White lines indicate slice locations. (Reprinted from IMRT Collaborative Working Group 2001.)

a) b)


5. METHODS AND TECHNIQUES FOR COMPREHENSIVE 3D DOSIMETRY 71

detector. While great strides have been made in this field, thedifficult challenge of obtaining high accuracy with transitdosimetry has limited its clinical use primarily to ruling outgross errors in daily patient radiotherapy treatment.

5.2 Methods of 3D Dosimetry

The term 3D dosimetry is commonly used, but it is rather non-specific. It is possible to obtain measurements in all threedimensions using many traditional dosimetry methods,including film, TLDs, ion chambers, diodes, etc. In earlyIMRT verification studies, quasi-3D dosimetry was achievedusing stacks of film in anthropomorphic phantoms (Bortfeldet al. 1994; Bortfeld 2006). However, isotropic and high-reso-lution 3D dosimetry is not readily achievable with these meth-ods without a prohibitive amount of effort. Here, we thereforerestrict the term 3D dosimetry to refer to dosimetry systemsthat can directly measure high-resolution isotropic dosimetrywithin a phantom. Some discussion of this definition wasgiven by Oldham et al. in the form of the Resolution-Time-Accuracy-Precision (RTAP) criteria (Oldham et al. 2001). TheRTAP represents a performance or capability goal for a 3Ddosimetry verification system to be viable for clinical use.Such a system should be able to deliver a 3D dosimetric anal-ysis of a treatment plan with 1 mm isotropic spatial resolutionin less than one hour with an accuracy of 3% and a precisionof 1%. This definition does rule out the semi-3D dosimetrysystems, such as the Delta4 (ScandiDos) and ArcCHECK®

(Sun Nuclear Corporation) devices, which contain planes orsurfaces of point detectors and rely upon interpolation to esti-mate a 2D or full 3D dose distribution (Létourneau et al.2004; Létourneau et al. 2009; Feygelman et al. 2011). Theseapproaches do, however, represent innovative commercialmomentum toward the ideal of a truly comprehensive 3Ddosimetry system. While these systems offer advantages interms of efficiency and convenience, they are not discussedfurther here due to the fact that they do not provide a fullythree-dimensional solution.

In the context described above, several true 3D dosimetrysystems are in current use, as illustrated in Figure 5–2. Thesesystems are all chemical dosimetry systems, comprised of amaterial which exhibits a physical response to radiation thatcan be quantified by an imaging or readout system. The vastmajority of work to date has been performed with threeclasses of materials: polymer gels, radiochromic gels, andradiochromic plastics. Typical gel agents include water-basedcomponents like gelatin or agarose. These three materials andtheir associated readout (imaging) methods are described inthe following sections. Recently, alternative systems for 3Ddosimetry that utilize scintillation (Beddar et al. 2009) or aCerenkov response to radiation exposure (Glaser et al. 2013)have been proposed. These systems are in the preliminary

phase of development, and therefore are not discussed furtherhere.

5.2.1 Materials

Polymer Gel DosimetryThe first 3D dosimetry work utilized the ‘BANG’ polymer gelformulation, in which the monomers acrylamide and N,N’-methylene-bis-acrylamide are mixed with aqueous gelatin(Maryanski et al. 1992; Maryanskit et al. 1994). These poly-acrylamide gels, or PAG gels, are commercially available asBANG® gels (MGS Research, Inc., Madison, CT). They arehighly tissue equivalent and exhibit a linear dose response(Baldock et al. 2010). The mechanism of their radiosensitivityis radiation-induced polymerization, as illustrated in Figure5–3. Free radicals generated in the gel during irradiation cre-ate reactive monomer ends which bind to neighboring mono-mer molecules in a polymerizing or cross-linking reaction,transferring the reactive end to the newly incorporated mole-cule. Polymer microparticles continue to grow until a termina-tion reaction occurs, either with a second reactive end orthrough cross-linking with an adjacent polymer chain. Thepolymerization reaction continues well after irradiation hasfinished, and often dosimeters are imaged approximately 24hours post-irradiation, when the gel is relatively stable. ThePAG thus contains radiation-induced microparticles, givingthe gel a cloudy or milky visual appearance where radiationhas been absorbed: the result of light scattering from the poly-mer microparticles. The number density of particles is propor-tional to the locally absorbed dose. The presence of theseparticles affects at least three physical aspects of the gelwhich can be quantitatively imaged: relaxivity of water pro-tons (MRI), attenuation of visible light (optical CT), andphysical density (x-ray CT). These methods of dose readoutare described in Section 5.2.2.

Figure 5–2. Currently available 3D dosimetry systems that arecapable of directly measuring 3D dose isotropically and withhigh resolution (2 mm or better), approaching the RTAP capa-bility criteria.



Several refinements have been introduced to the polymergel material system in the years since its first inception. Thesehave generally targeted improvements in four areas:

1. Decreasing the negative impact of oxygen. The radio-sensitivity of polymer gels is drastically reduced when oxy-gen is present in the gel because it prematurely terminates theradicalized polymer ends. This necessitates that gels must bemade in a deoxygenated environment, typically within a glovebox, and then set into an oxygen-impermeable container toprevent oxygen leaching into the gel over time. Investigatorshave typically employed glass or Barex™ plastics for this pur-pose. An alternative approach is to incorporate an oxygen-scavenging compound in the gel, such as ascorbic acid withcopper. Such a “MAGIC” gel was reported by Fong et al.(Fong et al. 2001) and was shown to be compatible with nor-mal lab oxygen conditions, removing the need for specializedoxygen prevention equipment.

2. Increasing the radiosensitivity of the gel. This can beachieved by increasing the monomer concentration, althoughdoing so may reduce the gel’s overall stability. The NIPAMgel has recently been optimized for higher sensitivity for usewith x-ray CT readout and low toxicity (Senden et al. 2006).

3. Creating lower-density, lung-equivalent gels. Theaccuracy of thoracic radiotherapy dosimetry is potentiallycompromised by the extreme density heterogeneities intro-duced by the lung, which has density on the order of 0.25 to0.33 that of muscle. 3D dosimeters may enable new methods

for both testing the accuracy of the dose predicted by treat-ment planning systems in and near the lung and also for veri-fying the uncertainty of radiotherapy delivery and the impactof respiratory motion. Currently, PAG gels are the only 3Ddosimetry material that has proven amenable to being manu-factured at densities low enough to achieve lung equivalence(De Deene et al. 2006).

4. Exploring the possible advantages offered by alterna-tive mechanisms of radiation-induced polymerization (Pappaset al. 2003; Baldock et al. 2010).

Fricke-based Gel Dosimetry The Fricke dosimeter (or ferrous sulphate dosimeter) has along history of use both as an absolute and a relative dosime-try system (Fricke and Morse 1927; Schreiner 2004). Thestandard Fricke dosimeter consists of small vials of ferroussolution containing Fe2+. The high water content and lowatomic number (Z) constituents render Fricke dosimeters tis-sue and water equivalent even for lower-energy radiationfields (Kron et al. 1993). When irradiated, Fe2+ is oxidized toFe3+, and the resulting proportion of Fe3+ (which is propor-tional to absorbed dose) is quantified by spectrophotometry(Scharf and Lee 1962). The standard Fricke dosimetry methodis effective, but the reaction is sensitive to temperature, andthe sensitivity is somewhat limited by the modest optical den-sity (OD) change of the Fe3+ ions at the probing light wave-length (224 nm). Imaging at such a short wavelength is

Figure 5–3. Polymer gel 3D dosimetry. a) Schematic indicating the mechanisms of radiation-induced polymerization (from Lepageand Jordan 2010). b) Photograph (left) and MRI image (right) of a BANG polymer gel in a glass sphere after irradiation with aGamma Knife® treatment (from Ibbott et al. 1997). c) Schematic illustrating how the final polymer microparticle structure dependsupon the gel composition (from Baldock et al. 2010). The four images in c) represent post-irradiation gel structure correspondingto monomer only (Aam); low initial bis crosslinker fraction, high bis fraction, and only bis crosslinker (no monomer).

a) b)

c)



feasible for optical cuvettes (path length 1 cm), but it is notfeasible to scale up for large gel volumes due to over-attenua-tion of the light.

3D Fricke-based dosimetry was first proposed by Gore etal. (Gore et al. 1984), who showed that ferric ions (Fe3+) havea greater influence on proton relaxation times than ferrousions (Fe2+), enabling the imaging of 3D dose distributions byMRI (Gore et al. 1984; Appleby and Leghrouz 1991). Thespin-lattice relaxation rate R1 was found to vary linearly withdose (Podgorsak and Schreiner 1992). R1 relaxivity measure-ment was preferred to spin-spin relaxivity (R2) for Fricke gelsbecause of its higher dynamic range (the unirradiated Frickedosimeter exhibits low R1) (De Deene 2010). A key limitationarises from the slow spatial diffusion of Fe3+ ions in the gel,leading to the practical limitation that the 3D distributionmust be imaged within 1 hour (Chu et al. 2000; Tseng et al.2002; de Pasquale et al. 2006). Early attempts to stabilize theFricke solution in gels were performed by a number of inves-tigators (Gore et al. 1984; Olsson et al. 1990; Hazle et al.1991; Olsson et al. 1992; Kron et al. 1993; Schreiner et al.1994). Initial studies reported low spatial resolution (thickslices) owing to the challenge of simultaneously obtaininglow noise with high spatial resolution using MRI. However,recent work employing fast 3D MRI sequences has shownpromising results: 1 mm isotropic resolution obtained in a 20-minute imaging session (Cho et al. 2013).

Access to MRI scanners is a restrictive aspect of MRI-based 3D Fricke dosimetry for many medical centers. Mucheffort has therefore been devoted to developing Fricke gels

that can be imaged by cheaper, benchtop optical systems. Theaddition of a metal ion indicator (e.g., xylenol orange) leadsto a visible color change in the presence of ferric (Fe3+) ions(Gupta et al. 1982). This development makes it possible tooptically image the radiochromic response of larger gel vol-umes using longer wavelength light with greater penetratingpower (Appleby and Leghrouz 1991). Kelly et al. (1998)demonstrated the feasibility of 3D optical CT dosimetry ofFricke-benzoic-xylenol (FBX) gels (see Figure 5–4). Theirsystem employed a scanning laser beam and was able toachieve sub-millimeter spatial resolution and an accuracy ofreconstructed attenuation values of within 2%, correspondingto a dose measurement accuracy of within 5% in the doserange 1 to 10 Gy. An important advantage of the FBX dosim-eter for optical CT dosimetry is the nature of the radiation-induced optical contrast. This is light-absorbing in nature, notscattering, so the amount of stray light in the dosimeter isminimal. The practical implications of the lack of optical scat-ter are significant, as it enables fast broad-beam scanning sys-tems may be utilized (Olding et al. 2010; Olding andSchreiner 2011). In practical terms, Fricke and FBX gels arerelatively easy and convenient to manufacture. Guidelineshave been provided by Jordan (2010). The gel is non-toxicand manufactured in a normoxic environment, eliminating theproblem of sensitivity to oxygen. The main challenges relateto the need for an external casing to support the gel (largely acost and convenience factor) and the time limitation (the gelmust be read or imaged within an hour of irradiation, prior tothe corrupting effects of diffusion).

Figure 5–4. a) Predicted dose distribution of a “4-fieldbox” irradiation technique (6MV and 4 × 4 cm). b) Cor-responding optical CT scan through an irradiated FBXgel. c) Line profile comparison along the line indicatedin a) and b). d) The change in absorbance spectrum ofan irradiated FBX dosimeter, indicating an optimal read-out wavelength of ~535 nm. (From Kelly et al. 1998.)

c)

d)a) b)



Radiochromic PlasticsPrior to 2005, 3D dosimetry studies were performed withwater-based gel materials. A novel radiochromic plastic mate-rial, Presage® was introduced in 2006 as a material compati-ble with 3D dosimetry by optical CT (Adamovics andMaryanski 2006). Presage consists of a firm polyurethanematrix doped with a halogenated hydrocarbon free radical ini-tiator and the leucodye leucomalachite green (LMG). Thepolyurethane matrix is highly transparent, significantly moreso than gelatin or agarose gels. Radiation-induced optical con-trast is generated through the oxidation of LMG to malachitegreen (Figure 5–5). Presage thus maintains the advantage ofradiochromic gels in the minimization of stray light throughan absorptive radiation-induced contrast mechanism. Thepolyurethane substrate is a hard plastic, removing the require-ment of an external casing to maintain the shape of the dosim-eter. Presage has proven exceptionally versatile in terms of itsability to be molded, with inclusion of embedded cavities andchannels (e.g., for brachytherapy) (Juang et al. 2013; Adam-son et al. 2012 and 2013). The feasibility of 3D printing ofPresage dosimeters of various shapes has also been recently

demonstrated, together with the facility for incorporatingpresage regions of different density (Bache et al. 2013).

The radiochromic response of the Presage dosimeter hasbeen demonstrated to be linear by many authors, up to highdoses (approximately 100 Gy), well beyond what is typicallyprescribed for clinical radiation therapy (Adamovics andMaryanski 2006; Guo et al. 2006 and 2006b; Sakhalkar et al.2009; Wang et al. 2010). These studies also reported negligi-ble energy or dose-rate dependence in the region 145 kVp to18 MV. A detailed study by Sakhalkar et al. (2009) showed agradual post-irradiation increase (or creep) of the optical den-sity in Presage, but this had no effect on the accuracy of therelative 3D dose distribution (i.e., the percentage of creep wasconstant at all dose levels). However, other studies havereported conflicting results as to the stability of the radiochro-mic response and the relative 3D distribution (Yates et al.2011). Substantial variations in the sensitivities of formula-tions from the same batch—and even the same batch but dif-ferent volumes—have been reported (Jackson et al. 2013). Thelatter effect, termed the volume effect, may arise from differ-ent cure rates of Presage cast into different-sized volumes. Thecuring of Presage involves an exothermic reaction, and the lin-

Figure 5–5. a) The molecular structure of the transparent leucodye leucomalachite green (LMG) and the absorbing oxidative prod-uct malachite green (from Adamovics and Maryanski 2006). b) Photograph of a cylindrical PRESAGE dosimeter (11 cm diameter),which inserts into a polyurethane head phantom for radiosurgery verification (from Thomas et al. 2013c). c) Post-radiation tempo-ral stability of the radiation sensitivity of several Presage variants, illustrating how minor changes in formulation can yield substan-tially different effects (from Juang et al. 2013). d) Linearity and stability of a Presage formulation.

a) b)

a) b)

c) d)



gering of heat in larger samples may result in Presage of dif-ferent hardness and sensitivity. These results suggest cautionwhen evaluating and using different Presage formulations. Thepolyurethane substrate’s constituent “part A” and “part B”components can be varied, in different proportions, to createdosimeters with markedly different hardnesses. Recent data(Juang et al. 2013) show wide variability in post-irradiationstability associated with relatively minor changes in polyure-thane components (Figure 5–5). When used for proton dosim-etry, under-response has been reported in the Bragg peak (Al-Nowais et al. 2009; Zhao et al. 2012), as is the case for manyother dosimeter materials (including PAGs and EBT film).

5.2.2 Dose Readout

Magnetic Resonance ImagingMRI was the first imaging modality utilized for 3D gel dosim-etry in the context of the quantitative R1 (spin-lattice) relax-ation of water molecules in Fricke gels. For Fricke gels, R1imaging is faster and has higher dynamic range than R2 (spin-spin) relaxation, owing to the low R1 values in unirradiatedgels. The mechanisms underlying the effects of paramagneticmolecules on relaxivity have been described in the literature(Gore et al. 1984; Podgorsak and Schreiner 1992). The mainlimitations to MRI 3D dosimetry of Fricke gels have been the

Table 5–1: Overview of important quantitative MR imaging sequences for R1 (= 1/T1), R2 (= 1/T2),and magnetization transfer ratio (MTR) imaging (from DeDeene 2010)

Sequence Type Conditions Variable Post-processing Availability Spatial

Accuracy

1. Quantitative R1 imaging sequences (R1 = 1/T1)

Single spin-echo(SE)

TE short TR(×2/×Ν)

Fit *** Very good

Saturation recovery(SRGE/SRSE)

TR long,TE short

TM(×2/×Ν)

Fit *** Good /Very good

Inversion recovery(IRGE/IRSE)

TR long,TE short

TI(×2/×Ν)

Fit *** Good /Very good

Driven Equilibrium Single Pulse Observation of T1 (DESPOT)

– FA(×2/×Ν)

Fit * Good

Look-Locker(LL, TOMROP)

FA small TI(×2/×Ν)

Fit * Good

Steady-state Free Precession (SSFP)

TR >> T2 FA(×2/×Ν)

Analytic/Fit ** Good

IR – Very fast acquisition (EPI, GRASE, HASTE)

TR long TI(×2/×Ν)

Fit ** Poor

2. Quantitative R2 imaging sequences (R2 = 1/T2)

Single spin-echo(SE)

TR long TE(×2/×Ν)

Analytic/Fit *** Very good

Fast spin-echo(FSE, TSE, RARE)

TR long TE(×2/×Ν)

Analytic/Fit *** Good

Multiple spin-echo (MSE, MC-SE)

TR long [ΔΤΕ (Ν)] Fit *** Very good

Steady-state Free Precession (SSFP)

TR >> T1

FA = 90°[2 echoes] Analytic ** Good

3. Quantitative magnetization transfer (MT) imaging sequences

MT pulse prepared spin echo imaging sequence

TR long MT pulse ampli-tude

Analytic ** Very good

Pulsed MT steady state TR short MT pulse ampli-tude

Analytic ** Good

Stimulated echo preparation – TM Analytic * Very good

The variable that is changed to acquire different contrast weighted images is shown in the third column. If the variable is varied automatically within the sequence, the parameter is shown between squared brackets. The meaning of the availability is as follows: * The imaging sequence is not provided by the manufacturer. The sequence should be developed in house.** The imaging sequence is available but significant changes to the imaging parameters are required.*** The imaging sequence is readily available on all clinical MRI scanners.



difficulty of generating low-noise images with high spatialresolution and the challenge of stabilizing the irradiated dosedistribution. The latter effect originates from the fact that thesmall Fe3+ ions can easily diffuse in gelatin or agarose gels(Schreiner 2004). The diffusion problem was solved with theintroduction of MRI polymer gel 3D dosimetry, where theradiation-induced polymer cross-linked microparticles areunable to move in the gel substrate (Maryanski et al. 1993).For polymer gels, R2 was found to be the preferred readoutquantity owing to a faster spin-spin exchange model (Mary-anski et al. 1993; Kennan et al. 1996; Baustert et al. 2000;Lepage et al. 2001, 2001b, Ceberg et al. 2012). In the absenceof oxygen contamination in the polymer gels, a linear doseresponse of R2 is observed below the onset of saturationeffects (Oldham et al. 1998b; Baldock et al. 2010). Imagingmagnetization transfer (MT) has also been found to be usefulfor low-density lung-equivalent gels (Lepage et al. 2002; Bal-dock et al. 2010).

From the above discussion, we can distinguish three fun-damental MRI parameters that are relevant for 3D dosimetryby MRI: spin-lattice relaxation rate (R1), spin-spin relaxationrate (R2), and magnetization transfer (MT). Whicheverparameter is chosen, it is essential that the appropriatesequence is implemented to ensure accurate determination. Alist of relevant MRI sequences is shown in Table 5–1 (from

De Deene 2010). A number of limitations and challenges havebeen identified for MRI 3D dosimetry, leading to a concernthat expertise in MR imaging be a prerequisite for accurate3D dosimetry (Vandecasteele and De Deene 2013b, 2013c,and 2013d). While some expertise is necessary, the prospecthas been greatly simplified by the recommendations in arecent report (De Deene 2010).

Optical CT Imaging Optical computed tomography appears to have arisen

independently and nearly simultaneously in three differentspecialty fields (Gore et al. 1996; Maryanski et al. 1996; Win-free et al. 1996; Sharpe et al. 2002; Sharpe 2004). The tech-nique of optical CT is analogous to the more familiar x-rayCT, except using visible light as the imaging radiation. In bothoptical and x-ray CT, line integrals of attenuation are acquiredat various views through the object to be imaged. The maindifferences include the methods of production and detectionof either the x-rays or visible light, and also the scanning con-figurations. The relatively small size of 3D dosimeters makesit practical to rotate the dosimeter rather than the source anddetector. The same mathematics (e.g., filtered back projectionor inverse radon transform) can be used to reconstruct eitherdata set. 3D maps of the local attenuation coefficients (x-rayor optical) are produced, and both methods are potentially

Figure 5–6. Optical CT scanning configurations. a) First-generation scanning laser (from Gore et al. 1996). b) Cone-beam CTarrangement (from Wolodzko et al. 1999). c) Parallel beam arrangement (from Krstajic et al. 2006). d) A fully bi-telecentric system(from Thomas et al 2011b).

a) b)

c) d)



susceptible to numerous artifacts, including stray radiation,rings, beam hardening, attenuation, motion, etc. (Oldham etal. 2003; Oldham and Kim 2004). For the purpose of 3Ddosimetry, several configurations of optical CT systems canbe identified and are illustrated in Figure 5–6. When com-pared with 3D dosimetry utilizing MRI, the primary advan-tages of optical CT are substantially reduced costs, increasedaccessibility, and potentially higher accuracy and precision inshorter imaging times (Oldham et al. 2001).

The first optical CT system was developed for polymergels, where the radiation-induced contrast is from polymermicroparticles which scatter (not absorb) light. The presenceof scattered light poses challenges to obtaining accurate opti-cal tomographic attenuation maps, analogous to the con-founding effects of x-ray scatter in cone-beam CT(Létourneau et al. 2005; Oldham et al. 2005). Accurate opticalCT is only feasible if the stray light can be prevented fromcorrupting the line-integral measurements in projectionimages. To counteract this effect, the first optical CT systemfor 3D dosimetry, the ‘OCTOPUS’ (Gore et al. 1996; Mary-anski et al. 1996), utilized a first-generation scanning laserconfiguration operating in a translate-rotate manner. In thisconfiguration, a laser beam is translated across a polymer geldosimeter, and each attenuation line profile is acquiredsequentially with a single photodiode detector. The dosimeteris then incrementally rotated in order to acquire the next pro-file. The first generation scanning configuration can be effec-tive at eliminating stray light from projection images throughthe utilization of a collimating aperture which restricts thelight acceptance on the detecting photodiode. Also, by acquir-ing each single line profile independently, it is impossible forstray light to contaminate neighboring line-attenuation mea-surements. These systems can thus be used to image dose indosimeters with a high scattered light component, like PAGS(Xu et al. 2004; Baldock et al. 2010). Several groups haveinvestigated the performance of the OCTOPUS (Islam et al.2003; Xu et al. 2004; Guo et al. 2006; Lopatiuk-Tirpak et al.2008). Variations on the scanning laser system were alsoexplored (Kelly et al. 1998; Oldham et al. 2001).

The limitation of the first generation laser scanning con-figurations is that long imaging times are needed to translateand rotate the dosimeter to acquire all of the necessary lineprofiles. Early works reported scan durations of several hoursfor large volumes (Gore et al. 1996; Oldham et al. 2001; Islamet al. 2003; Campbell et al. 2013). More recent scanning lasersystems have achieved faster speeds by up to a factor of four(Campbell et al. 2013; Qian et al. 2013). Still faster scanningspeeds are possible utilizing rotating mirrors to translate thelaser beams (Krstajic and Doran 2007). These latter systemsrequire sophisticated motion control and data acquisition cali-bration and coordination due to the nonlinear laser motion.For smaller samples, good quality results have been reported

(Doran et al. 2010; Abdul Rahman et al. 2011; Doran et al.2013).

Despite the advances in scanning laser systems, it was notuntil the advent of broad-beam scanning systems that the pos-sibility of 3D dosimetry systems that could yield results inclinically acceptable time frames (per the RTAP criteria)became feasible. The first prototype broad-beam optical CTscanners were proposed at the turn of the millennium(Wolodzko et al. 1999; Doran et al. 2001). The image qualityfrom these first systems was not suitable for practical use, aresult compounded by the fact that radiochromic (low-scatter)dosimeters were not then readily available for optical CT.Other groups also developed in-house broad-beam systemswith more sophisticated components and configurations;Babic et al. 2008; Sakhalkar and Oldham 2008; Olding et al.2010).

At the present time, two categories of fast broad-beamoptical CT scanning configurations can be identified: parallel-beam and cone-beam, illustrated in Figure 5–6. Cone-beamCT systems have the advantage of reduced cost, but the poten-tial disadvantage of lower accuracy due to their susceptibilityto stray light artifacts (Oldham 2006; Babic et al. 2009; Old-ing et al. 2010; Wuu and Xu 2010; Olding and Schreiner2011). Parallel-beam systems, and in particular telecentricsystems, are more expensive due to their sophisticated lenses,but they have the capacity for higher accuracy since theyeffectively remove the stray light component (Krstajic andDoran 2007b; Sakhalkar and Oldham 2008). A debate hasensued as to the relative merits of these two approaches. Straylight artifacts have been reported when using cone-beam CTscanners and polymer gels, as might be expected due to thehigh light scatter component (Olding et al. 2010; Olding andSchreiner 2011). A continued improvement in the sophistica-tion and image quality of broad-beam optical CT scanners isevident in the literature (Wolodzko et al. 1999; Doran et al.2001; Krstajic and Doran 2006; Krstajic and Doran 2007b;Babic et al. 2008; Sakhalkar and Oldham 2008; Olding et al.2010; Thomas and Oldham 2010; Olding and Schreiner2011).

A candidate for the current state-of-the-art for optical-CT3D dosimetry is a powerful large field-of-view matched bi-telecentric scanning system (Thomas et al. 2011b). This is thefirst broad-beam system that was commissioned and bench-marked for clinical use, and the high-quality data it deliveredset a new standard for 3D dosimetry. Accompanying papersaddressed what turned out to be minor corrections associatedwith stray light reflections (mostly within the lenses) andspectral artifacts (Thomas et al. 2011 and 2011c). These cor-rections are negligible except under certain extreme condi-tions (e.g., small field output factor and percent depth-dosecommissioning measurements).



Other 3D Dosimetry Readout MethodsReadouts from MRI and optical CT account for the majorityof 3D dosimetry work conducted to date. However, otherreadout methods have been explored. The most promising isx-ray CT of polymer gels (Hilts et al. 2000; Trapp et al. 2001;Hilts et al. 2005; Koeva et al. 2009). The underlying radiation-induced contrast mechanism is an increase in the mass densityof irradiated gel in the range of 1 mg/cm3/Gy (or a fewHounsfield Units per Gy). With such a relatively low sensitiv-ity, maintaining sufficient signal-to-noise with adequate spa-tial resolution becomes challenging. Gel formulations withimproved sensitivity and increasingly sophisticated filteringand imaging protocols have been developed (Jirasek et al.2010; Chain et al. 2011; Kakakhel et al. 2011; Jirasek et al.2012; Johnston et al. 2012). In recent work (Johnston et al.2012), it was shown that IMRT 3D verification was feasiblewith an x-ray CT 3D dosimetry system utilizing a gammapass/fail criteria (3%, 3 mm) which yielded a 93.4% passingrate over the entire treated volume. Other readout techniqueswhich have been investigated for PAG gels include ultrasound(Mather and Baldock 2003) and Raman imaging (Rintoul etal. 2003).

5.3 Applications of 3D Dosimetry

The immediate concern driving the early development of 3Ddosimetry came from the field of radiation therapy. The key

need was to find a way to verify complex therapeutic mega-voltage (MV) dose distributions in a more comprehensivemanner than is possible with conventional planar (e.g., film)or point detectors (ion chambers, TLDs, etc.). Tremendousprogress has been achieved, and there are now several 3Ddosimetry systems that can achieve and surpass the RTAP per-formance goal described in Section 5.2. It is not surprisingthen that the majority of applications of 3D dosimetry to daterelate to the verification of advanced therapy treatment tech-niques. Examples are listed below, and the utility of 3Ddosimetry is further illustrated in figures 5–7 through 5–9.

• intra-cranial radiosurgery (Olsson et al. 1992; Oldhamet al. 2001; Novotny et al. 2002; Sandilos et al. 2006;Babic et al. 2009; Clift et al. 2010; Wang et al. 2010;Gopishankar et al. 2011; Cho et al. 2013; Oldham et al.2013; Thomas et al. 2013c;

• stereotactic body radiotherapy (Cosgrove et al. 2000;De Deene et al. 2006; Brady et al. 2010; Olding et al.2013);

• 3D conformal therapy (Ibbott et al. 1997; De Deene etal. 1998; De Deene et al. 2000);

• IMRT verification (Oldham et al. 1998; Gustavsson etal. 2003; Vergote et al. 2003; Wuu and Xu 2006; Babicet al. 2008; Sakhalkar et al. 2009b; Pavoni et al. 2012;Vandecasteele and De Deene 2013);

Figure 5–7. Clinical utility of 3D dosimetry to investigate the accuracy of a new treatment technique: a single isocenter, multiplelesion, VMAT radiosurgery treatment of intra-cranial brain lesions. (From Thomas et al. 2013c.)



• volumetric-modulated arc therapy (VMAT) (Vergote etal. 2004; Babic et al. 2008; Ceberg et al. 2010; Thomaset al. 2013c);

• respiratory gating techniques (Ceberg et al. 2008;Lopatiuk-Tirpak et al. 2008; Brady et al. 2010; Thomaset al. 2013);

• image-guided therapy (Thomas et al. 2013c; Rankineand Oldham 2013b);

• deformable cumulative dosimetry (Yeo et al. 2012;Juang et al. 2013b);

• patient-specific dose-volume estimations: a distin-guishing advantage of 3D dosimetry is the facility torelate quality assurance data to likely clinical signifi-cance for the patient (Oldham et al. 2012);

• characterizing and commissioning brachytherapysources, both HDR (Schreiner et al. 1994; McJury et al.1999; Wai et al. 2009; Pierquet et al. 2010; Palmer etal. 2013) and LDR (Adamson et al. 2012; Adamson etal. 2013); and

• verification of proton deliveries (Bäck et al. 1999; Al-Nowais et al. 2009; Zhao et al. 2012; Kroll et al. 2013).A remaining challenge is that most systems exhibit anunder-response in the Bragg peak.

It is informative to consider how 3D dosimetry is utilizedin the majority of cases listed above, including its correspond-ing strengths and limitations. In many verification studies,such as that illustrated in Figure 5–7, the end result is a com-parison between a predicted (or planned) dose distributionagainst a measured 3D dose distribution. A straightforwardqualitative comparison in the traditional three orthogonalplanes can be effective at determining gross differences, andcan be made visually, using either color wash dose maps (Fig-

ure 5–7) or by comparing isodose lines (Figure 5–8). Often,however, a more quantitative evaluation is required, such asthat provided by a gamma map analysis (Low and Dempsey2003), as illustrated in Figure 5–7c. The gamma metric con-tains two criteria: a dose-difference criteria (DD) and a dis-tance-to-agreement criteria (DTA). The gamma map isconstructed by evaluating the gamma metric at each point inthe experimental distribution. The advantage is that the agree-ment between the two distributions can be characterized by asingle number. Typically, the passing rate—which refers tothe percentage of points in the target distribution for whichthe gamma metric is less than unity—is the reported figure ofmerit. Gamma pass rates can be calculated on individualplanes (Ezzell et al. 2009) or in a full 3D calculation. The lat-ter represents a comprehensive metric taking full account ofthe agreement between the two distributions in three dimen-sions. Whenever a gamma map analysis is presented, it isimportant to note the magnitudes of the criteria used, whethera minimum threshold dose level was included (above whichgamma is calculated), and whether the dose criteria is a localor global percentage. The presence of significant noise in adistribution can also impact the utility of gamma evaluation(Low and Dempsey 2003; Low et al. 2011; Schreiner 2013).Common gamma criteria values in current use are 3%,3mm,as proposed in the AAPM TG Report 119 (Ezzell et al. 2009).However, these values have recently been criticized as toogenerous, with the potential to allow clinically significanterrors to pass undetected (Nelms et al. 2011; Nelms et al.2013). In practice, many authors now include a range of pass-ing rates calculated with different criteria.

The strengths of a comprehensive 3D verification capa-bility are readily apparent. Oldham et al. recently describedtwo key advantages from a 3D dosimetry quality-assurance

Figure 5–8. a) Evaluation of the end-to-end accuracy of image-guided delivery (IGRT) of four independent deliveries of the treat-ment shown in Figure 7 (from Thomas et al. 2013c). These plots show the average and one std-dev variability of key isodose lines,averaged over the four independent deliveries, in the three principle views: a) axial, b) coronal, and c) sagittal. Isodose lines of 95,90, 80, 70, 50, and 30% are shown. There are three lines for each isodose: the middle solid line is the mean isodose (averagedover all dosimeters) and the dashed lines on either side represent the 1σ variation of that isodose line.

a) c)b)



(QA) procedure: treatment verification is comprehensivethroughout the whole treated volume, and the clinical signifi-cance of deviations can be assessed through the generation ofdose-volume histogram curves and dose overlays on thepatient’s anatomy (Oldham et al. 2012). Both steps representdevelopments that advance the clinical relevance of complextreatment QA. However a limitation of cumulative 3D dosim-etry verification is that when deviations are identified, it is dif-ficult to identify the cause of the deviation from the 3Dmeasurement. Other dosimetry tools are required to isolatethe origin of the deviation to, for example, a specific treatmentfield.

In addition to the clinical applications described above,the techniques of 3D dosimetry have also found useful appli-cations in the pre-clinical world and in non-medical special-ties. A rapidly expanding field of radiation therapy andbiological research involves the precise delivery of miniatureradiation therapy dose distributions to small animal models.Precise and accurate delivery are key to achieving successful

trial data. Examples include commissioning a micro-irradiator(Newton et al. 2011) and the evaluation of end-to-end accu-racy of IGRT micro-radiotherapy treatment (Rankine et al.2013b). Extremely high-resolution 3D dosimetry measure-ments have also been demonstrated for use in characterizingsmall and novel x-ray systems (Doran et al. 2010; Doran et al.2013). In the field of radiation protection and the nuclearindustry, 3D dosimetry techniques have been proposed andinvestigated as efficient diagnostic methods to determinepotential radiation contamination sources (Farfán et al. 2010;Oldham et al. 2010; Farfán et al. 2012; Stanley et al. 2012).

5.4 Summary and Recent Developments

3D dosimetry has proven to be a highly innovative field ofresearch and clinical development for over 20 years. The orig-inal motivating factor (developing more comprehensive meth-ods for verification of complex radiation therapy treatments)is even more relevant today, due to the seemingly endlessincrease in the sophistication and complexity of modern

Figure 5–9. Illustration of an important advantage of 3D dosimetry: the facility to estimate the likely clinical impact to the patient ofany delivery errors detected in 3D measurements in phantoms. (From Oldham et al. 2012.)



radiotherapy treatments. Current areas of continued innova-tion and further development can be identified in three majorareas: materials development, readout development, and novelapplications. In materials development, the main challengesare to develop more stable dosimeters for remote credential-ing activities and to produce reusable dosimeters for improvedeconomics within an institution (Juang et al. 2013). In addi-tion, new classes of potential dosimeters have emerged frommicelle technology (Jordan and Avvakumov 2009; Nasr et al.2013; Vandecasteele and De Deene 2013). Polymer gels arealso being developed with enhanced sensitivity for x-ray CT(Jirasek et al. 2010). The development of a 3D dosimetrymaterial that does not exhibit an LET dependence is also anactive area of research (Lopatiuk-Tirpak et al. 2012; Zhao etal. 2012). An interesting recent advancement is the use ofnovel 3D printing technology to create anatomically accurate3D dosimeters (Bache et al. 2013).

For 3D dosimetry readout, researchers are pursuingimproved optical CT scanner designs and protocols that arefaster, more accurate (reduced scatter), cheaper, and withhigher resolution (Olding and Schreiner 2011; Thomas et al.2011b). Optical CT scanning is typically performed with thedosimeter submerged in a fluid that shares the same refractiveindex in order to eliminate refraction/lensing artifacts at theboundary of the dosimeter, but scanning configurations whichrequire substantially less (or even no) fluid matching are cur-rently being investigated (Doran and Yatigammana 2012;Ramm et al. 2012; Rankine and Oldham 2013). MRIsequences that minimize problematic sample heating whilestill preserving low noise and higher spatial resolution arealso under development (Vandecasteele and De Deene 2013,2013b). For x-ray CT readout, more sensitive formulations arebeing evaluated (Jirasek et al. 2012; Johnston et al. 2012).

A review of the field at this time reveals strong progresstoward the long-sought goal of a reliable, practical, and cost-effective 3D dosimetry system that can match the RTAP crite-ria (Section 2). Several systems have demonstrated in labora-tories that they can meet this goal, but these systems have notyet been realized in the commercial world. This is likely tooccur in the next few years, and it will represent an importantcomponent to strengthening core QA practices in radiationtherapy, contributing to safer and more accurate treatment ofour patients.

5.5 Acknowledgments

I am grateful to John Schreiner for kindly proofreading andcommenting on this article. I am especially grateful to themany students, post-docs, and colleagues who have workedwith me on 3D dosimetry topics over the years. There are toomany to mention, but without fail it has been a privilege anddelight to work with you all.

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