Comparative study of linear andcurvilinear ultrasound probes to assessquadriceps rectus femoris muscle massin healthy subjects and in patients withchronic respiratory disease

S Mandal,1,2 E Suh,1,2 A Thompson,1,2 B Connolly,1,2,3 M Ramsay,1,2 R Harding,1

Z Puthucheary,4 J Moxham,3 N Hart1,2,3

To cite: Mandal S, Suh E,Thompson A, et al.Comparative study of linearand curvilinear ultrasoundprobes to assess quadricepsrectus femoris muscle massin healthy subjects and inpatients with chronicrespiratory disease. BMJOpen Resp Res 2016;3:e000103. doi:10.1136/bmjresp-2015-000103

Received 2 August 2015Revised 17 October 2015Accepted 19 October 2015

1Lane Fox Clinical RespiratoryPhysiology Research Centre,St Thomas’ Hospital, Guy’s &St Thomas’ NHS FoundationTrust, London, UK2Division of Asthma, Allergyand Lung Biology, King’sCollege London, London, UK3Guy’s and St Thomas’ NHSFoundation Trust and King’sCollege London, NationalInstitute of Health ResearchComprehensive BiomedicalResearch Centre, London, UK4Division of Respiratory andCritical Care Medicine,University Medicine Cluster,National University HealthSystems, Singapore

Correspondence toDr S Mandal;swapnamandal@hotmail.com

ABSTRACTIntroduction: Ultrasound measurements of rectusfemoris cross-sectional area (RFCSA) are clinicallyuseful measurements in chronic obstructive pulmonarydisease (COPD) and critically ill patients. Technicalconsiderations as to the type of probe used, whichaffects image resolution, have limited widespreadclinical application. We hypothesised that measurementof RFCSA would be similar with linear and curvilinearprobes.Methods: Four studies were performed to compare theuse of the curvilinear probe in measuring RFCSA. Study 1investigated agreement of RFCSA measurements usinglinear and curvilinear probes in healthy subjects, and inpatients with chronic respiratory disease. Study 2investigated the intra-rater and inter-rater agreementusing the curvilinear probe. Study 3 investigated theagreement of RFCSA measured from whole and splicedimages using the linear probe. Study 4 investigated theapplicability of ultrasound in measuring RFCSA during theacute and recovery phases of an exacerbation of COPD.Results: Study 1 showed demonstrated no difference inthe measurement of RFCSA using the curvilinear andlinear probes (308±104 mm2 vs 320±117 mm2, p=0.80;intraclass correlation coefficient (ICC)>0.97). Study 2demonstrated high intra-rater and inter-rater reliability ofRFCSA measurement with ICC>0.95 for both. Study 3showed that the spliced image from the linear probewas similar to the whole image RFCSA (308±103.5 vs263±147 mm2, p=0.34; ICC>0.98). Study 4 confirmedthe clinical acceptability of using the curvilinear probeduring an exacerbation of COPD. There wererelationships observed between admission RFCSA andbody mass index (r=+0.65, p=0.018), and betweenRFCSA at admission and physical activity levels at 4weeks post-hospital discharge (r=+0.75, p=0.006).Conclusions: These studies have demonstrated thatclinicians can employ whole and spliced images fromthe linear probe or use images from the curvilinearprobe, to measure RFCSA. This will extend the clinicalapplicability of ultrasound in the measurement of musclemass in all patient groups.

INTRODUCTIONB-mode ultrasound imaging is a widely usedtechnique. More recently, its clinical use hasbeen extended to the assessment of periph-eral skeletal muscle wasting, with single andsequential measurement of the quadricepsrectus femoris (RF) muscle cross-sectionalarea (RFCSA).

1–5 RFCSA has been shown tocorrelate with volitional measures of quadri-ceps strength1 2 and this approach has char-acterised peripheral muscle wasting inpatients with chronic obstructive pulmonarydisease (COPD).1 2 This non-volitional tech-nique, with high levels of intra-rater andinteroccasion reliability,1 3 4 6–8 has beenemployed by us and by others, as a tool toassess skeletal muscle wasting in critically illpatients.3 9 Despite these supportive data,there are limitations to the use of this ultra-sound method.

KEY MESSAGES

▸ These studies have shown that a curvilinearultrasound probe is as effective as a linear ultra-sound probe in measuring the rectus femoriscross-sectional area.

▸ Additionally, splicing images using a linear ultra-sound probe can also be used to measure therectus femoris cross-sectional area if anadequately sized linear probe or a curvilinearprobe is not available.

▸ Furthermore, using a curvilinear ultrasoundprobe to the measure rectus femoris cross-sectional area in a cohort of patients with anexacerbation of chronic obstructive pulmonarydisease has demonstrated a correlation betweenthe rectus femoris cross-sectional area, andactivity.

Mandal S, Suh E, Thompson A, et al. BMJ Open Resp Res 2016;3:e000103. doi:10.1136/bmjresp-2015-000103 1

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Conventionally, a higher frequency (6–10 MHz) linearultrasound probe has been used to measure RFCSA, asthe high resolution permits clear definition of theborder of the quadriceps rectus femoris muscle.10

However, the linear ultrasound probe has limited depthpenetration and imaging window width,1 10 which canadversely affects the reliability and reproducibility of themeasurement. For example, in young critically ill traumapatients with substantial peripheral muscle bulk onadmission,3 in those morbidly obese patients withincreased subcutaneous fat and in fluid overloaded crit-ical care patients, the image window width and depthlimits acquisition of the whole RFCSA image. In contrast,the lower frequency (2–5 MHz) curvilinear ultrasoundprobe has greater depth penetration10 and windowwidth but lower resolution,10 which has raised concernsabout its usefulness when measuring RFCSA.Recent systematic reviews evaluating the use of muscle

ultrasound for measurement of peripheral skeletalmuscle reported a paucity of studies investigating theeffect of frequency and resolution on muscle area mea-surements.11 12 Indeed, previous studies comparing theuse of linear and curvilinear ultrasound probes havebeen inconclusive, with one study suggesting that theremay be a bias towards larger measurements with a linearprobe,13 and another demonstrating similarity betweenthe probes.14 One previous study has directly comparedthe linear and curvilinear probes to measure cross-sectional area, albeit this was a non-clinical study usingvessels filled with different density media as the simula-tion model.15

In the current study, we hypothesised that there wouldbe no difference in RFCSA measurements using a linearand curvilinear ultrasound probe between healthy sub-jects and patients with chronic respiratory disease,including interoperator and interoccasion measure-ments using the lower frequency probe. Additionally wehypothesised that spliced images using the linear probewould provide similar RFCSA whole image measurement.Finally, we assessed the clinical feasibility of using thelower frequency curvilinear probe in patients withCOPD during the acute and recovery stage of anexacerbation.

METHODSSubjectsEthical approval for the study was obtained from thelocal ethical review board (Westminster NationalResearch Ethics Committee). All healthy subjects andpatients provided written and informed consent.Healthy volunteer subjects were recruited from labora-tory and clinical staff. Patients with stable chronicrespiratory disease undergoing assessment for initiationof home mechanical ventilation were recruited from theLane Fox Respiratory Unit, St Thomas’ Hospital,London, UK, and patients with COPD were recruitedduring hospital admission for an acute exacerbation.

Validation studiesFour separate validation studies were performed.▸ Study 1 investigated the agreement of RFCSA mea-

sured using linear and curvilinear probes at two-thirdand three-fifth of the distance between the anteriorsuperior iliac spine (ASIS) and the superior borderof the patella, in healthy subjects and in patients withstable chronic respiratory disease (n=32).

▸ Study 2 investigated the intra-rater and inter-rateragreement using the lower frequency curvilinearprobe. Intra-rater reliability measurements were madein 10 healthy subjects who had RFCSA measurementstaken at two-third and three-fifth the distancebetween ASIS and the superior border of the patellaon two separate occasions using the curvilinear ultra-sound probe, within 10 days of each other, by oneoperator (SM). Inter-rater reliability measurementswere made in 10 participants with chronic respiratoryfailure (7 with COPD and 3 with obesity hypoventila-tion syndrome), who had RFCSA measurements per-formed on the same day by two independentoperators (SM and AT), using the curvilinear ultra-sound probe. For each patient, each operator tookthree measurements at two-third and at three-fifthdistance from ASIS to superior boder of the patella.

▸ Study 3 investigated the agreement of RFCSA measuredfrom whole and ‘spliced’ images using the higher fre-quency linear probe in healthy subjects and in thosewith stable chronic respiratory failure (n=32).

▸ Study 4 investigated the clinical applicability of ultra-sound measurements using the lower frequency curvi-linear probe to track the change in RFCSA and, inparticular, to investigate the relationship betweenchanges in RFCSA and physical activity, during theacute and the recovery phases of an exacerbation ofCOPD (n=18).

RFCSA measurement protocolWhole image aquistion—RFCSA was measured at two-thirdand three-fifth distance from ASIS to the superiorborder of the patella. The patient was placed in a semi-recumbent position with a pillow under the knee. Theprobe was placed perpendicularly to the long axis of thefemur, as previously reported, with minimal change inthe angle of the probe.1 16 17 The operator positionedthe probe on the surface of the thigh to avoid distortingthe underlying tissue. Measurements were taken in astandardised manner—RFCSA measurements were takenby the liner probe first and then by the curvilinearprobe. Real-time, B-mode ultrasound images wereacquired using a 6 MHz linear probe with a 38 mm array(Sonosite S-ICU, SonoSite Inc, Japan) and 2–5 MHzcurvilinear probe with a 60 mm array (Sonosite S-ICU,SonoSite Inc). The mean value of three consecutivemeasurements of RFCSA using each ultrasound probewas recorded.Spliced image aquistion—Whole and matched ‘spliced’

RFCSA images were acquired using the linear ultrasound

2 Mandal S, Suh E, Thompson A, et al. BMJ Open Resp Res 2016;3:e000103. doi:10.1136/bmjresp-2015-000103

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probe at both two-third and three-fifth distance. RFCSAmeasurements were calculated off-line using the Image Jprogram (National Institutes of Health, Maryland, USA).Both operators took images sequentially and then ana-lysed results off-line at a later date so as to be blinded tothe results. Spliced measurements involved taking twoimages, one of each half of the RF muscle, at the samepoint, for example, at three-fifth distance, one image ofthe lateral half of the RF muscle and at the same pointan image of the medial half of the RF muscle. A land-mark within the muscle was used as the point at whicheach half of the muscle would be measured so as toavoid overlapping of the images (figure 1). The twomeasurements of each half of the muscle (lateral andmedial) were summated to provide the overall ‘splicedimage’ cross-sectional area.

Physical activity measurementA subset of patients admitted with an acute exacerbationof COPD (AECOPD) also wore a uniaxial accelerometeractivity monitor (Actiwatch Spectrum, PhillipsRespironics, Murraysville, Pensylvania, USA) during theirhospital admission, to assess the relationship betweenchanges in RFCSA and physical activity.18–21 Patients wererequested to wear the accelerometer for the duration ofhospital stay as well as for 28 days following hospital dis-charge. Participants were asked to wear the accelerom-eter for 24 h/day. Data for inpatient admission wereincluded if the accelerometer was worn for a minimumof 3 days and at least for 10 h during the daytime toallow assessment of physical activity. For follow-up data,an average of 7 days of data was used to assess physicalactivity.

Statistical analysisResults are presented as mean±SD, unless otherwisestated. Statistical analysis was performed using Prism V.6(Graphpad, California, USA). Independent t tests and

Bland-Altman analysis were used to compare the twomodes of scanning, and intraclass correlation coeffi-cients (ICC) were calculated to determine agreementbetween the two methods.

RESULTSStudy 1: RFCSA agreement between the linear andcurvilinear probeParticipantsFifty consecutive participants were enrolled (37 healthysubjects and 13 patients with chronic respiratoryfailure). Participants were not excluded on the basis ofbody mass index (BMI). Of those with chronic respira-tory failure, 12 had COPD and 1 had restrictive lungdisease. The ages of the healthy cohort and chronicrespiratory failure cohort were 36±9 and 72±10 years,respectively.

Whole RFCSA image acquisition using the linear andcurvilinear probesThirty-two participants had whole RFCSA image aquisi-tion using the linear probe visualised at the two-thirdand 14 at three-fifth distance from the ASIS and patella(figure 2A, B), the remaining 18 and 36 participants,respectively, could not have their RFCSA wholly visualisedwith the linear probe. The main reason the musclecould not wholly be visualised at three-fifth distance wasdue to the muscle being too large to fit the width of theprobe. However, all participants had whole RFCSA imageaquisition using the curvilinear probe. The age of these32 participants was 49±21 years (patient cohort (n=13)72±10 years; healthy cohort 32±4 years).

RFCSA agreement measured at two-third distance from ASISand superior border of the patellaThere was no difference between RFCSA measurementsusing the linear and curvilinear probes at two-third dis-tance from ASIS and superior border of the patella (308±104 mm2 vs RFCSA 320±117 mm2, 3.8% difference;p=0.80). The ICC was 0.97 (table 1). Bland-Altman ana-lysis of linear and curvilinear RFCSA measurementsdemonstrated the majority of values within the 95% con-fidence limits of −62.4 to 39.4 with a bias of −11.6±26.0 mm2 (figure 3A). The mean coefficient of vari-ation (CV) was 2.6% for linear images and 2.6% forimages taken with the curvilinear probe.

RFCSA agreement measured at three-fifth distance from theASIS and superior border of the patellaThere was no difference between RFCSA measurementstaken using the linear and curvilinear probes (327±103vs 334±117 mm2, 2.1% difference p=0.93) at three-fifthdistance from the ASIS and superior border of thepatella with an ICC of 0.98 (table 1). CV for wholelinear images was 2.3% and 2.2% for images taken withthe curvilinear probe. Bland-Altman analysis demon-strated a bias of −7.0±22.2 mm2 (figure 3B) with allFigure 1 A representative example of imaging splicing.

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values lying within the 95% confidence limits (−50.5 to36.5).

Comparison of healthy subjects and patient cohort attwo-third distance from ASIS to the patellaAt two-third distance from ASIS to the patella, the RFCSAmeasurement in the patient cohort was 246±79 vs 251±85 mm2 for linear and curvilinear probes, respectively(2.0% difference), with CVs of 2.7% and 4.1%. The ICCfor these measurements was 0.98. For the healthy sub-jects the measurements taken using the linear and curvi-linear probes were 351±97 and 366±115 mm2 (4.3%difference), respectively. The CV for the linear probemeasurements was 2.7% and for curvilinear probe 2.4%,with an ICC of 0.95.

Study 2: Intra-rater and inter-rater agreement of RFCSAmeasurement using a curvilinear probeParticipantsTen healthy subjects were recruited, eight females (32±6 years) with RFCSA measurements performed on twoseparate occasions.

Intra-rater agreementRFCSA at two-third distance from ASIS to patella at visit 1was 558±141 mm2 and at visit 2, 549±129 mm2 (1.6% dif-ference), with a CV of 2.5%. At three-fifth distance fromASIS and patella, the RFCSA for visit 1 was 699±164 mm2

and for visit 2, 703±164 mm2 (0.5% difference), with

a CV of 2.6%. Overall, the ICC for all measurements,at two-third and three-fifth distances, was 0.98(operator SM).

Inter-rater agreementTen patients with chronic respiratory failure wererecruited, including five males (70.2±10.3 years) with aBMI of 33.6±8.9 kg/m2. At two-third distance, the RFCSAwas 531±249 mm2 (operator SM) and 513±215 mm2

(operator AT), demonstrating a 3.4% differencebetween the two measurements, with respective CVs forthe measurements of 4.1% and 4.0%, and an ICC of0.88. At three-fifth distance, there was no difference inRFCSA measurements between the two operators, foroperator SM, the mean RFCSA was 672±249 mm2 and foroperator AT, 672±302 mm2, with CVs of 3.6% and 7.9%,respectively. The ICC was 0.98. Bland-Altman analysisdemonstrated satisfactory agreement between the opera-tors (figure 3C). The overall ICC, using RFCSA data fromthe two-third and three-fifth distances, was 0.95.

Study 3: RFCSA agreement measured from whole andspliced images using the linear probeParticipantsComparison of the whole and spliced image RFCSAmeasurement using the linear probe from the healthysubject and patient cohorts in study 1 was performed(n=32).

Figure 2 Rectus femoris

cross-sectional area (RFCSA)

image acquired using (A) linear

ultrasound probe at two-third

distance (same subject) and (B)

curvilinear ultrasound probe at

two-third distance (same subject).

Table 1 RFCSA measurements taken by linear and curvilinear probes

Group Linear Curvilinear ICC p Value

2/3 distance

n=32

308±104 mm2 320±117 mm2 0.97 0.8

3/5 distance

n=14

327±103 mm2 334±117 mm2 0.98 0.93

ICC, intraclass correlation coefficient; RFCSA, rectus femoris cross-sectional area.

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RFCSA measured at two-third distance from ASIS andsuperior border of the patellaThere was no difference between the whole and splicedRFCSA measurements taken using the linear probe (308±104 vs 263±147 mm2, 14.6% difference; p=0.34), withan ICC of 0.98. CV was 3.1% for spliced linear images.Bland-Altman analysis of whole and spliced linear RFCSAmeasurements demonstrated the majority of values werewithin the 95% confidence limits of −188.4 to 262.4,with a bias of 37.0±115.0 mm2 (figure 3D).

RFCSA measured at three-fifth distance from ASIS andsuperior border of the patellaThere was no difference between the whole and splicedlinear RFCSA images (321±144 vs 327±103 mm2, 1.9% dif-ference; p=0.82), with an ICC of 0.99. CV was 5.4% forthe spliced images. Bland-Altman analysis demonstrateda bias of 15.1±88.5 mm2, again with the majority of

values lying within the 95% confidence limits (−158.5 to188.6 mm2, figure 3E)With retrospective analysis, a difference was demon-

strated in the time taken to perform the scans using thespliced method compared to using whole image acquisi-tion (3.3±1.5 min vs 1.5±0.9 min, p=0.002).

Study 4: To investigate the relationship between RFCSAand physical activity during the acute phase and recoveryphase of an exacerbation of COPDPatientsSeventeen patients were recruited. Baseline character-istics are reported in table 2. RFCSA was measured within48 h of admission to hospital and at 4 weeks post-discharge. RFCSA measurement at admission was 536±310 mm2 at three-fifth the distance and 427±249 mm2

at two-third the distance from ASIS to patella, measuredusing a curvilinear probe. At neither the three-fifth

Figure 3 (A) Bland-Altman plot of linear probe and curvilinear probe rectus femoris cross-sectional area (RFCSA) measurements

at two-third distance from anterior superior iliac spine and patella. (B) Bland-Altman plot of linear probe and curvilinear probe

RFCSA measurements at three-fifth distance from anterior superior iliac spine and patella. (C) Bland-Altman plot of two

independent operator measurements of RFCSA using a curvilinear probe at three-fifth distance from anterior superior iliac spine

and patella. (D) Bland-Altman plot of whole and spliced RFCSA measurements using linear probe at two-third distance from

anterior superior iliac spine and patella. (E) Bland-Altman plot of whole and spliced RFCSA measurements using linear probe at

three-fifth distance from anterior superior iliac spine and patella.

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distance (−9±230 mm2, 4.8%; p=0.67) nor at thetwo-third distance (−22.4±158 mm2, 0.6%; p=0.52) wasthere change in RFCSA between admission and follow-upat 4 weeks.

Relationship between physical activity and RFCSA duringAECOPDSixteen of the participants underwent triaxial accelerom-eter activity monitoring during hospital admission andduring the 4-week follow-up period after discharge.There was a direct correlation observed between admis-sion RFCSA (532±319 mm2) and BMI (24.8±7.7 kg/m2;r=+0.65, p=0.018, figure 4A), and between RFCSA atadmission (532±319 mm2) and activity levels at 4 weekspost-hospital discharge (activity count 150 610±91 006AU; r=+0.75, p=0.006). Interestingly, there were no corre-lations observed between RFCSA at admission and age,length of stay or exacerbation frequency. At 4 weeks post-hospital discharge, 12 patients had continued to wearthe accelerometer, with a direct relationship observedbetween: RFCSA (409±192 mm2) and activity count(180 735 ±78 702 AU; r=+0.76, p=0.006, figure 4B); andRFCSA and BMI (r=0.58, p=0.04). There were no correla-tions observed between forced expiratory volume at 1 sand age, or activity levels.

DISCUSSIONThe current study has demonstrated that, despite thetechnical limitations of using the lower frequency

curvilinear ultrasound probe, particularly in terms ofimage resolution, the measurement of RFCSA using thecurvilinear probe has satisfactory agreement with themeasurement obtained using the standard higher fre-quency linear probe. The curvilinear probe demon-strated superiority over the linear probe, as it was able toacquire, on every occasion, the whole RFCSA imagewhereas this was not possible using the linear probe,especially in patients with substantial muscle bulk andexcess subcutaneous fat. Furthermore, fewer wholeRFCSA images were acquired by the linear probe at three-fifth distance from the ASIS to the superior border ofthe patella compared to two-third distance, and the clin-ician should consider using the lower frequency curvilin-ear probe when using the three-fifth landmark distance.In addition, the curvilinear probe was shown to have sat-isfactory inter-rater and intra-rater agreement, which hasconfirmed the clinical usefulness of the curvilinearprobe. Moreover, the inter-rater and intra-rater RFCSAagreement of the curvilinear probe was greater at three-fifth distance, and this further supports the use of thelower frequency curvilinear probe at three-fifth distancefrom the ASIS to the superior border of the patella.There was no difference between the spliced and wholeimage measurement of RFCSA when using the linearprobe, albeit it must be acknowledged that the differ-ence between the whole and spliced images was less atthree-fifth distance from ASIS to the superior border ofthe patella, and thus, if the clinician uses the splicedimage, the three-fifth distance would be preferred.Finally, the curvilinear probe has clinical acceptability tomonitor the trajectory of change of RFCSA in patientswith COPD during the acute and recovery stage of anexacerbation.

TECHNICAL IMPLICATIONS OF THE STUDYImage acquisition using the curvilinear probe showedsatisfactory inter-rater, intra-rater and interoccasion reli-ability. This is consistent with a previous non-clinicalstudy that investigated the differences between the curvi-linear and linear ultrasound probe using fluid-filledvessels as the test objects. In the study by Warner et al,

Table 2 Baseline characteristics of COPD exacerbation

cohort

Age (years) 71±10

Gender (M:F) 10:6

BMI (kg/m2) 24.8±7.7

Admission FEV1 (L) 0.7±0.2

Admission FVC (L) 1.5±0.5

Length of stay (days) 6.2±7.0

All values are mean±SD.BMI, body mass index; COPD, chronic obstructive pulmonarydisease; F, female; FEV1, forced expiratory volume in 1 s; FVC,forced vital capacity; M, male.

Figure 4 (A) Correlation between rectus femoris cross-sectional area (RFCSA) at admission and body mass index. (B)

Correlation between RFCSA at admission and activity at 4-week follow-up.

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the intra-rater and inter-rater reliabilities were high,however, the differences in measurements between thetwo probes varied with the simulation and the model ofultrasound machine employed, albeit the difference wassmall at <50 mm2. Furthermore, in agreement withHammond et al,8 we have shown high intertransducer,inter-rater, intra-rater and intraoccasion agreement. Itmust be highlighted, however, that the study byHammond et al8 was performed on a small group of par-ticipants and, surprisingly, the measurements were per-formed at three-fourth the distance between the ASISand superior border of the patella, a distance that hasnot been validated against quadriceps muscle strength,quadriceps muscle endurance, exercise capacity or otherclinical variables, unlike the three-fifth and two-third dis-tances.1–3

The current study has demonstrated that the splicingmethod could be the technique to use if an adequatelysized linear probe or curvilinear probe is not available,and that this technique can be used in healthy, chronicand acute patient populations. In addition, the measure-ments of RFCSA by linear and curvilinear ultrasoundprobes are not significantly different, as demonstratedby the small differences between measurements, highICC and low CV. The ICC using the curvilinear probeand splicing images using a linear probe was 97%, indi-cating that both techniques could be used to measureRFCSA in patients in whom a linear probe is unable tovisualise the whole area of the muscle. This is whollyrelevant to the RFCSA measurement at three-fifth dis-tance from ASIS to the superior border of the patella, asfewer whole RFCSA images were acquired by the linearprobe at this landmark.

CLINICAL IMPLICATIONSSimilarity between measurements of the RFCSA usingdifferent techniquesThese findings have demonstrated that RFCSA measure-ments obtained using three different methods (linearwhole images, spliced linear images and images from acurvilinear probe) are equally effective in measuringRFCSA, with the understanding that using a linear orcurvilinear probe is preferential to the splicing method,due to the greater variability in measurements with thismethod. Indeed, the present data support the use of thelower frequency curvilinear probe at three-fifth distancefrom ASIS to superior border of the patella. This is clin-ically important since respiratory and critical care depart-ments will have an ultrasound available for venous lineinsertion and pleural ultrasound with at least one of theprobes available. Furthermore, in clinical cases wheresequential or follow-up scans are required, these should,based on the current data, be performed with the sameprobe. This has particular clinical utility in the measure-ment of RFCSA in patients with high muscle mass, such asyoung critically ill trauma patients, and patients with anincreased subcutaneous layer such as caused by fluid

overload and obesity, where depth penetration as well asan extended window width are required.

Application in the acute settingUltrasound has previously been used to monitor changesin RFCSA in the critically ill,3 to measure response toresistance training in COPD and healthy subjects,22 andto correlate RFCSA with muscle strength.1 These studieshave all used a linear probe. To the best of our knowl-edge, this is the first study to use a curvilinear probe totrack changes in RFCSA. Although the study numberswere small in the acute exacerbation cohort, these pre-liminary data are novel and hypothesis generating. Inaddition to demonstrating that the curvilinear ultra-sound probe can be used to track changes in acutelyunwell patients with COPD, we have shown correlationsbetween RFCSA at admission and body composition aswell as the level of physical activity at 4 weeks. Indeed, ina subgroup of these patients, we observed a direct posi-tive relationship between RFCSA and physical activity at4 weeks following hospital discharge. This approachcould have clinical importance in patient selection, toidentify those acute patients most likely to benefit fromrehabilitation, which may, in part, explain the lack ofimprovement with rehabilitation in a recently publishedtrial on these patients.23 24 Additionally, Greening et al25

showed that RFCSA was associated with readmission andmortality following admission with an exacerbation ofCOPD, which highlights the requirement to have robustmeasures to track the change in RFCSA during an exacer-bation. The data we have presented from four studiesperformed in this paper were detailed physiologicalstudies, and it is interesting that there were no correla-tions between RFCSA and frequency of exacerbations; thismay have been due to small sample size—larger studieswill be required to confirm or disprove these findings.

Limitations of the studyIn contrast to CT and MRI, which are relatively operatorindependent, ultrasound is an operator-dependent modeof imaging and errors in measurements can occur.However, we have shown in the current study that theultrasound images obtained, using both, the linear andcurvilinear probes were similar, with high intra-rater andinter-rater agreement with both probes. This wasachieved, in part, by the scans being performed by twoexperienced operators and, in particular, attention wasfocused on ensuring an optimal standardised operatingprotocol for measurement acquisition including avoid-ance of muscle compression, and accurate probe positionperpendicular to the long axis of the femur. A major limi-tation of the spliced image method acquired using thelinear ultrasound probe was that it required increasedtime for image acquisition compared to the whole imageacquisition technique. This extended time requirementis also likely to apply to image analysis time, however, thiscalculation was not possible retrospectively. There was nodifference in the time taken to obtain images using a

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curvilinear probe compared to a linear probe, but therewas, as expected, a difference between using the curvilin-ear probe and linear splicing method. Although the dif-ference in RFCSA measurements using the splicedmethod at two-third distance was not significant, the dif-ference was larger than those obtained using the othermethods. While the authors acknowledge that there wasa difference in the spliced measurements at two-third dis-tance from ASIS to the superior border of the patella,this difference was not present at the three-fifth distance,and as there is no currently established minimal clinicallyimportant difference (MCID) for change in RFCSA,further research is required to determine the MCID invarious patient groups. Finally, we acknowledge thatthere was a difference in the width of the probes, whichresulted in fewer whole images being captured by thelinear probe, albeit that this probe has been commonlyused in previous studies.1 3 12 26 The authors acknow-ledge that the shape of the probe will influence theability to image the underlying muscle in detail, however,the linear probe is currently the most common probeused in practice. These current data support the use ofthe splicing technique employing the linear probe, if acurvilinear probe is not available, and that the measure-ment should be taken at three-fifth distance. The authorsacknowledge that the sample sizes were small and futurework is required to confirm these data in large popula-tions, particularly, looking at the correlations in theCOPD population, sample size calculations will need tobe calculated in order to detect differences.

CONCLUSIONIn healthy subjects and patients with chronic respiratorydisease, the data from these detailed physiologicalstudies have demonstrated that the use of the lower fre-quency curvilinear probe is not inferior to that of thehigher frequency linear probe in measuring RFCSA.Furthermore, there was strong intra-rater and inter-rateragreement in the use of the curvilinear probe tomeasure RFCSA. The RFCSA spliced image method haslimitations and it should only be used when a curvilinearprobe is not available, and the clinician should use thesame method to measure RFCSA when acquiring sequen-tial follow-up data. The use of the curvilinear ultrasoundprobe has been validated in both, stable and acutepatients with chronic respiratory disease, which willpermit extension of the use of the curvilinear probe topatients where the image depth pentration and widthcapture requirements are greater, such as young traumapatients with high muscle bulk, morbidly obese patientswith significant subcutaneous fat and patients with fluidoverload.

Contributors SM and NH designed the study. SM, ES, AT and RH wereinvolved in data collection. SM was responsible for data analysis. SM, ES, AT,RH, MR, BC, ZP, JM and NH were involved with drafting and in review of themanuscript.

Competing interests None declared.

Patient consent Obtained.

Ethics approval Westminster National Research Ethics Committee.

Provenance and peer review Not commissioned; externally peer reviewed.

Data sharing statement No additional data are available.

Open Access This is an Open Access article distributed in accordance withthe Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, providedthe original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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