European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 161–165

Measurement of uterine fibroid volume: a comparative accuracy andvalidation of methods study

Stephen D. Quinn a,1, John Vedelago b,*, Elika Kashef b,1, Wadyslaw Gedroyc b,1,Lesley Regan a,1

a Department of Obstetrics and Gynaecology, St. Mary’s Hospital, Praed Street, London W2 1NY, United Kingdomb Deparment of Radiology, Imperial College London, St Mary’s Hospital, Praed Street, London, United Kingdom

A R T I C L E I N F O

Article history:

Received 13 January 2013

Received in revised form 16 August 2013

Accepted 21 August 2013

Keywords:

Uterine fibroids

Focused ultrasound

Leiomyoma

Validation

Measurement accuracy

A B S T R A C T

Objective: A range of measurement techniques have been described which may be used to calculate

uterine fibroid volume. A commonly-reported method involves application of a formula for the volume

of an ellipsoid sphere to three orthogonal axes of a fibroid as measured on cross-sectional images. We

aimed to compare this method and a second method, that of software-computed parallel planimetric

uterine fibroid computation on MRI images, to a gold standard: the volume of objects measured by water

displacement. We also compared these methods in volume estimation of patient fibroids using MRI data.

Study design: Mixed observational study and blinded cross-sectional analysis of imaging data.

Results: Large inter-observer variability was noted when using the ellipsoid formula method, which was

also inaccurate when compared to the gold standard. Conversely, the parallel planimetric method

showed excellent interobserver correlation and a high degree of correlation with gold standard volume

measurements.

Conclusion: We conclude that the parallel planimetric method, although a more complex and time

consuming technique, is the more accurate and therefore preferred method for measuring uterine fibroid

volume.

� 2013 Elsevier Ireland Ltd. All rights reserved.

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology andReproductive Biology

jou r nal h o mep ag e: w ww .e lsev ier . co m / loc ate /e jo g rb

1. Introduction

The size, shape and MRI signal intensity of uterine fibroids, themost common tumour affecting women, varies considerably. Thismakes measuring the volumes of these tumours particularlyproblematic. The size of fibroids and uteri has often been describedby either their maximum diameter, or volume calculated by theellipsoid formula or the parallel planimetric area method (Cavalierimethod) [1–6]. The ellipsoid formula estimates the volume of anobject by assuming an ellipsoid shape, whereas the parallelplanimetric area method calculates a volume based on the sum ofthe multiple areas recorded on either MRI or computerizedtomography (CT) images, multiplied by the thickness of eachindividual slice. An interpolation formula is then applied bysoftware to smooth the boundaries of the object between slices,

* Corresponding author. Tel.: +44 7796 284 834/2033126666;

fax: +44 20331 21123.

E-mail addresses: Stephen.quinn@imperial.nhs.uk (S.D. Quinn),

John.vedelago@imperial.nhs.uk, John_vedelago@yahoo.com (J. Vedelago),

Elika.kashef@imperial.nhs.uk (E. Kashef), w.gedroyc@imperial.ac.uk (W. Gedroyc),

l.regan@imperial.ac.uk (L. Regan).1 Tel.: +44 2033126666.

0301-2115/$ – see front matter � 2013 Elsevier Ireland Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.ejogrb.2013.08.036

and at the peripheral margin of the object, a feature which moreaccurately simulates the true shape of the object. It is common forstudies investigating treatment of fibroids to measure volumebefore and after treatment of fibroids, but if different measurementtechniques are in use, it is important for radiologists andgynaecologists to understand how accurate and comparable thesetechniques are.

This study was therefore conducted in two parts. Firstly, weaimed to compare (a) the parallel planimetric area and (b) ellipsoidformula to (c) a gold standard (that of volume of water displaced byan object) to assess the relative accuracy of each method, using avariety of organic objects simulating potential tumour or uterineshape. We also concurrently assessed the inter-observer variabilityof these measurements as part of this evaluation. Secondly, wecompared the inter-observer correlation of the parallel planimetricarea method in estimating the volumes of a variety of randomlychosen fibroid uteri and non-perfused volumes after MR-guidedfocused ultrasound treatment.

2. Materials and methods

The volumes of 50 different, irregularly shaped objects werecalculated using the water-displacement method. To reproduce

Fig. 1. Organic objects measured by volume displacement.

Fig. 2. Planimetric software trac

S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 161–165162

the organically irregular shape of fibroids, a variety of differentlyshaped fruit and vegetables were measured (potatoes, courgettes,plums, apples, and avocados) (Fig. 1). The volume of normal salinedisplaced by the objects was calculated using a 1000 ml plasticmeasuring cylinder with 5 ml gradations. Following this, all objectswere scanned using a GE 1.5T MRI (GE Healthcare, Milwaukee,USA) and tri-planar T2 weighted images obtained. MRI wasperformed within 4 h of the volume displacement measurements.

The volume of an ellipsoid object (v) was calculated as: v = 4/3pabc where a, b and c are the maximum diameters in threeorthogonal planes. To calculate the volume using the ellipsoidmethod, the maximum diameter of each object in three separateplanes was recorded for each object using T2 weighted images andthe volume calculated using the formula above.

The MRI images were then uploaded into a software package forplanimetric volume assessment, GE Reportcard�. Using thissoftware the area of each slice was calculated by assigningmultiple points on each sagittal slice around the perimeter of theobject and a total object volume calculated automatically by theprogramme using the software’s interpolation formulae (Fig. 2).

Following this initial assessment, the T2-weighted tri-planarMR images of 50 women with uterine fibroids, obtained at 1.5 T

e outline of organic object.

Fig. 3. (a) Sagittal MRI image of uterine fibroid post focused ultrasound ablation treatment. (b) Outline of non perfused volume of fibroid (traced in green) using parallel

planimetric method to determine non-perfused volume.

Table 1Bland Altman plot of two observers (SQ and JV) measuring volume of displacement

of a variety of organic objects. X axis: volume measured; Y axis: average difference

of means.

0 50 100 150 200 250 300

-6

-4

-2

0

2

4

6

Average of VolDisJV and VolDisSQ

Vo

lDis

JV

- V

olD

isS

Q

Mea n

0.0

-1.96 SD

-4.3

+1.96 SD

4.3

S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 161–165 163

and undergoing treatment with magnetic resonance guidedfocused ultrasound ablation, were then examined by twoindependent investigators (SQ and JV) at different times. Eachinvestigator was blinded to the other’s results. Each observer usedthe parallel planimetric method to calculate the total uterinevolume (TUV), volume of the largest fibroid (VolFib), and final non-perfused volume following administration of the gadoliniumcontrast agent post-procedure. The area of uterus, fibroid and NPVwas marked on each sequential sagittal slice. The total volume wasautomatically calculated by the Reportcard� software, summationof the adjacent volumes and application of interpolation formulaebetween slices (Fig. 3).

2.1. Statistical analysis

The inter- and intra-observer agreement was calculated usingthe coefficient of variation. Statistical graphs and calculation wereproduced using MedCalc Software Version 12.1.0 – � 1993–2011.The degree of agreement between different methods of volumecalculation was assessed according to the method of Bland andAltman [7,8], plotting the difference between each result vs. themean of the two results. Pearson correlation coefficients were alsoused to compare measurements made by the two readers, andlinear regression was used to obtain the individual slope and 95%confidence intervals (CI). A p-value of less than 0.05 wasconsidered statistically significant. Data analysis was performedusing commercially available software (SPSS 19, Chicago, IL, USAand GraphPad Prism 5.0, CA, USA).

3. Results

3.1. Comparison of volume of water displacement with the parallel

planimetric method and ellipsoid method: organic objects

The range of volumes measured in the 50 objects (fruit andvegetable) group was 35–270 ml as measured by the volumedisplacement method. The correlation between observers record-ing the volume of water displaced by the objects was veryfavourable. The difference between the volumes calculated by twoobservers, a radiologist (JV) and a gynaecologist (SQ), was plottedagainst the mean of their two results. The volume calculated usingthe displacement method by JV (VolDisJV) and the volumecalculated using the displacement method by SQ (VolDisSQ) isshown in Table 1. In all cases, the difference between the observed

volumes fell between 1.96 standard deviations of the mean(0.0 ml). From this we concluded that there was no significantdisagreement between investigators when using the volumedisplacement method.

The mean difference was 0.01 ml, with 95% confidence intervals(CI) of �0.6101 to 0.6301 and a standard deviation (SD) of 2.1818.The mean volume calculated by SQ and JV for each object was usedas the gold standard by which we assessed the other methods ofvolume calculation.

We then compared this mean volume obtained using the waterdisplacement method to the parallel planimetric method, andconstructed a Bland–Altman plot. The mean difference betweenthese groups was 2.63 ml, with 95% confidence intervals (CI) of1.92 to 3.34 and a standard deviation (SD) of 2.58. Conversely, incomparing the mean volume of the water displacement methodwith the mean volume of the ellipsoid method a mean difference of�16.08 ml, with 95% CI of 9.97 to 22.19 and an SD of 22.05 wasobserved.

The range and mean of each method is reported in Table 2. Inshort, the planimetric method was, by a considerable margin, the

Table 2Measurements by SQ and JV by alternative methods.

Uterine volume SQ Uterine volume JV Fibroid volume SQ Fibroid volume JV NPV SQ NPV JV

Mean (ml) 726.60 725.67 314.76 319.76 138.87 140.98

Standard deviation 383.31 386.02 266.19 275.76 96.83 99.03

Range (ml) 216.20–1905.30 220.30–1894.00 25.20–1169.40 26.00–1201.00 7.40–529.70 10.00–524.30

S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 161–165164

method which showed, by both range and mean, the closestapproximation to the ‘gold standard’ volume of water displaced.

3.2. Inter and intra observer variability assessment

We performed seven pairwise comparisons of method, firstlycomparing the results between investigators for each method, andthen for each observer between their volume calculations by thedisplacement, parallel planimetric, and ellipsoid methods respec-tively (Table 3).

There was very little variability between observers whenmeasuring the volume of each object by the water displacementmethod as shown by Pearson correlation reported in Table 3. Therewas also very good correlation within each individual observerbetween the volume measured by water displacement and thevolume as measured by the planimetric method. Very good inter-observer correlation using the planimetric method was observed.Conversely, the ellipsoid measurements resulted in markedlydifferent volume calculations between observers. Further, thosevolumes obtained using the ellipsoid method were not at all wellcorrelated with the ‘true’ volume as measured by water displace-ment.

3.3. Utility of parallel planimetric method in fibroid measurement

As we had found excellent correlation between observers inusing the parallel planimetric method measuring organic objects,and excellent correlation of this method with the gold standard ascalculated by volume of water displaced, we proceeded to utilizethis method to calculate fibroid volume in 50 patients selected at

Table 3Correlation between volume of displacement, parallel planimetric and ellipsoid metho

Comparison Mean differencea Pearson

correlation

Volume displacement method JV vs. SQ �0.05 � 4.59 0.997

Reportcard method JV vs. SQ �0.28 � 6.59 0.993

Ellipsoid method JV vs. SQ �0.4 � 20.3 0.882

Volume displacement vs. Reportcard

SQ 2.52 � 4.14 0.997

JV 2.75 � 3.14 0.998

Volume displacement vs. ellipsoid method

SQ 15.90 � 28.75 0.879

JV 16.25 � 19.06 0.957

a Data are means � SD.

Table 4Range, mean difference and correlation of uterine and fibroid volume measurement be

Comparison Range (ml)

n = 50

Mean

differencea

Pears

correl

Uterine volume calculation JV vs. SQ 220.3–1905.3 0.93 � 19.85 0.99

Fibroid volume calculation JV vs. SQ 25.2–1201.0 5.24 � 16.45 0.998

NPV JV vs. SQ 7.4–534.3 2.11 � 9.01 0.996

a Data are means � SD.

random. The results of this second part of our study are given inTable 4. Pearson correlation was excellent between observers foruterine volume, fibroid volume and non-perfused volume. Asexpected, the standard deviation of bias was greatest in the uterinevolume calculations where the range of values was the largest.

4. Comments

Whilst clinical symptomatology is the primary concern afterfibroid therapy, accurate measurement of uterine fibroid volume isdesirable for a variety of reasons. Accurate volume measurement isof importance in the assessment of fibroids being considered foruterine-sparing treatments such as focused ultrasound therapy orlaparoscopic myomectomy and in the comparison of studiesevaluating treatment options. Large fibroids may be considered arelative contra-indication for focused ultrasound therapy orlaparoscopic myomectomy. Excessively rapid growth of a lesionmay raise suspicion of more sinister non-leiomyoma pathology, orindicate earlier follow-up or intervention. The irregular margins ofa fibroid following focused ultrasound therapy may make volumemeasurement based on a simple three-axis calculation not a truereflection of the complexity of the structure. Monitoring theefficacy of medical hormonal therapy also relies on accurate serialdetermination of fibroid and uterine volume.

Our results suggest that, although it is the quickest and mostsimple method available, there is wide inter-observer variabilitywhen using the ellipsoid method of volume calculation, and that,further, it often does not reflect the true volume of an irregularovoid structure. This significant degree of inter-observer variabili-ty could lead to inaccurate assessment of fibroid volume, growth or

ds between two observers (JV and SQ).

P value

(two tailed)

Bland Altman analysis

Bias SD of bias 95% limits of agreement

0.000 0.05 4.58 �8.94 to 9.04

0.000 0.28 6.593 �13.20 to 12.64

0.000 0.40 20.3 �40.19 to 39.39

0.000 2.52 4.138 �5.59 to 10.63

0.000 2.75 3.145 �3.414 to 8.39

0.000 15.91 28.73 �40.41 to 72.22

0.000 16.26 19.06 �21.10 to 53.61

tween two observers (SQ and JV) using parallel planimetric method.

on

ation

P value

(two tailed)

Bland Altman analysis

Bias SD of bias 95% limits of agreement

0.000 �0.92 19.85 �39.82 to 37.97

0.000 5.24 16.46 �27.01 to 37.50

0.000 2.11 9.01 15.56 to 19.77

S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 161–165 165

regression, before or after therapy. This finding may be ofparticular relevance to fibroid volume calculations obtained usingultrasound images, which are generally performed using theellipsoid method. On the basis of our results, we contend that theoptimum method of pre- and post-treatment fibroid volumeassessment is the planimetric method using T2-weighted MRIimages.

The planimetric method has been validated in volumemeasurement of other structures and organs in the body, includingmeasurement of the chambers of the heart and the prostate [9,10],and has been used to measure fetal, placental, prostate and uterinevolume [1,11,12]. Validation studies have been performed usingboth ultrasound and MRI modalities.

A potential disadvantage of the planimetric technique isthe amount of time required to calculate the volume of anobject using this method. On each slice, multiple pointsoutlining the perimeter of the object must be marked withcallipers manually, until the entire perimeter has beencircumnavigated and defined. This represented the mosttime-consuming part of the process; in our experience theplanimetric method may take many times longer than thesimple application of a prolate formula to three diameters inthe x, y and z axes. In the future, software advances whichautomatically define the perimeter of an object may be ofadvantage in streamlining this process, and allow theradiologist or gynaecologist to perform the volumetriccalculation in a fraction of the time currently required.

Our study was limited by several technical constraintswhich could have potentially introduced small, and we believeinsignificant, sources of error. The interpolation algorithm ofthe software defines the outline of an object between twopoints which have been marked manually by the observer onthe perimeter of the object. Depending on where these pointsare defined, and how many, we noticed that occasionally theautomatically calculated trace of the outline of the object couldbe drawn deep to its surface, leading to a potential underesti-mation of its volume. Irregular edges or margins of certainobjects would exacerbate this effect. We endeavoured to re-draw any instances where this occurred. When measuring thevolume of water displacement, we were also unable toconfidently perform measurements to the nearest millilitreusing the measuring flask, because the gradations on the side ofthe flask were at 5 ml intervals. Our measurements representedour best interpretation, taken at the horizontal limit of themeniscus of fluid, to the nearest millilitre. Such potentialsources of error, we believe, are very minor when compared tothe differences between two observers using the formula for anellipsoid volume. Defining exactly which measurement pointsconstitute a fibroid’s largest dimensions, at which angles suchmeasurement lines should be drawn and on which slices andplanes, are all factors open to wide inter- and intra-observervariation and, we suggest, account for the large degree ofvariation between the two observers noted in our study.

5. Conclusion

Although relatively time-consuming and requiring dedicatedsoftware, we contend that the parallel planimetric method is likelyto be more accurate in estimating uterine fibroid volume, and closelyreflects the true volume of an object. Fibroid size followingultrasound ablation therapy or embolization is an often-quotedmeasure of a fibroid’s response to treatment; accurate determina-tion of size is therefore important in comparing studies quotingvolumetric parameters. Following focused ultrasound ablation oruterine fibroid embolization, an important measurement is the non-perfused volume (NPV) of the fibroid tissue, which is often of anirregular shape. The NPV, in particular, is best suited to the parallelplanimetric area method. A variety of measurement techniques havebeen reported in measuring fibroid growth and response to therapy;our results indicate that calculating the volume of uterine fibroidsusing the formula for an ellipsoid sphere is considerably lessaccurate and could introduce error into results. We thereforerecommend the planimetric method using T2-weighted MRI imagesas the most accurate and consistent measurement technique forfuture studies investigating fibroid size.

Conflict of interest statement

No conflict of interest is declared.

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