Musculoskeletal Research Laboratories

Department of Orthopedic Surgery

Yong Loo Lin School of Medicine

Email: dosbs@ nus.edu.sg

MRI SET UP (Ref: usa.healthcare.siemens.com)

MRI CHANGES IN LOWER LIMBS IN TRANSITION TO FRAILTY: A PROSPECTIVE STUDYStacey KH Tay1, Subhasis Banerji1, Reshma Merchant2, Effie Chew2, Gautam Singh1, Ravi Kambadur3, Mridula Sharma4, Barry Perreira5, Chueh Loo Poh6

Sarcopenia is a loss of muscle mass and strength associated with aging. It is one of the

key concerns in an aging population because of progressive loss of function associated

with other concomitant processes such as neuromuscular impairment, poor nutrition and

loss of mobility associated with frailty. This cumulative decline of muscle mass may

precede loss of function and mobility and the objective of this study was to identify early

markers of sarcopenia in aging men by evaluating MRI qualitative and quantitative

changes of the lower limb muscles.

The study population consisted of 50 healthy-weight, non-smoker community dwelling men.

Thirty elderly men aged 60 – 80 years were recruited. Control groups included 10 healthy

young men aged 21 – 30 years and 10 middle aged healthy men aged 40 – 50 years.

Chronic diseases such as diabetes mellitus with HbA1C above 8 and presence of

complications such as retinopathy, nephropathy and peripheral vascular disease were

excluded. Drug use such as steroids, testosterone and growth hormone were part of the

exclusion criteria. These men were recruited from May 2010 – June 2012 and informed

consent was obtained under National Healthcare Group Domain Specific Research Board

ethics approval.

Study participants underwent fine slice (7 mm) MRI imaging (Siemens HDx 3 Tesla Twin

Speed) of both lower limbs. Images were post-processed with in-house algorithm for

quantitation of muscle (fig. 1) and quantitation of extra-muscular fat volume as well as

texture analysis for approximation of intramuscular fat infiltration. Individual muscles were

also quantified (fig. 2). Study participants underwent questionnaire survey of typical diet,

exercise level, physical evaluation of muscle strength with handgrip dynamometer testing,

muscle function with 6 min timed walk, timed up-and-go and an evaluation of frailty (a

clinically validated frailty scale Canadian Study of Health and Ageing (CSHA), fig. 3), Of the

elderly age group, 10 were in CSHA 1 and CSHA 2 (fit and well), 10 were in CSHA 3

(managing well with minimal chronic disease) and 10 were in CSHA 4 (vulnerable)

categories.

This study identified several markers of sarcopenia in pre-frail elderly patients, namely loss of muscle volume, a distinctive posterior muscle group wasting as

well as an increase in intramuscular fat infiltration in elderly men progressing on towards frailty. Posterior muscle wasting could arise due to changes in gait,

sedentary lifestyle, or certain catabolic mechanisms occurring later in life. These findings identify a specific muscle wasting associated with aging and frailty,

and may indicate a target for exercise intervention (especially hamstring and gastrocnemius muscles) to improve stability, mobility and healthy aging. Increased

fat infiltration also suggests that fat may not be an inert bystander in the sarcopenic process but, as an inflammatory tissue, may play a role in worsening

sarcopenia in the elderly. Further studies will be needed to evaluate this hypothesis.

Grant Support: National Research Foundation, Singapore

1Department of Paediatrics, National University of Singapore, 2Department of Medicine, NUS, 3School of Biological Sciences, Nanyang Technological University, 4Department of

Biochemistry, NUS, 5Department of Orthopaedic Surgery, NUS, 6School of Chemical and Biomedical Engineering, NTU.

Introduction

Methodology

Results

Conclusion

Abstract ID: BP-CR-02

• There was a significant decrease in the absolute volume of the lower limb muscle mass,

with preferential wasting of the posterior compartment muscles (hamstring and

gastrocnemius muscles) (fig. 4). Loss of muscle mass, especially of the posterior

compartment antigravity muscles constituted one of the observable early signs of

sarcopenia.

• There was significant correlation between the CSHA groups versus grip strength and

other parameters of muscle function such as the 6 m walk and timed up-and-go tests

(data not shown).

• Poorer muscle volume was also associated with increased sway during walking and

standing, likely to indicate poorer stability and increased risk of falls .

• In the comparison across muscle groups, intramuscular fat infiltration was another sign

of early frailty (fig. 5). There was a net increase in fat infiltration associated with

progressively frailer categories of elderly subjects across all major muscle groups in the

lower limbs, that was statistically significant. The degree of fat infiltration was also more

marked in the posterior compartment muscles.

• Interestingly, fat infiltration was already apparent even in the healthy middle-aged

control group of men, indicating that accumulation of fat may be a very early sign of

aging, although it is unclear in this group if the fat infiltration is secondary to muscle

wasting or due to decreased physical activity (sedentary lifestyle) and higher BMI.

Email: stacey_tay@nuhs.edu.sg

*This study was supported by National Research Foundation-Competitive Research, Grant Ref. no: NRF-CRP 3-2008-4, (Singapore) and was conducted at National University Hospital, Singapore

Fig. 1 Muscle volume quantitation was performed on serial transverse images of lower limbs 100 cm above and 100

cm below the knee joint. Manual segmentation of the transverse images was performed for muscle, bone, fat and

connective tissue elements. Intramuscular fat infiltrate volume was then subtracted after bias correction using a custom-

designed algorithm to obtain final muscle volume.

Fig 4. (A) Healthy individuals with minimal intramuscular fat infiltrates and good

muscle bulk. (B) Pre-frail individuals who had normal muscle function based on grip

strength and functional testing but showed early signs of loss of muscle volume,

increased extra-muscular fat volume and increased intramuscular fat infiltration. (C)

Frail individuals who had poor muscle function based on grip strength and functional

testing with associated replacement of wasted muscle with extra-muscular fat and

severe fat infiltration in posterior compartment musclesFig. 5 Chart showing the fat infiltrates versus total muscle and intramuscular fat volume. Dark blue bars denote healthy

young 20-30y males, red bars denote healthy middle-aged 40 – 50 y males, green bars denote healthy elderly 60 – 80y

males (CSHA 1-2), purple bars denote well managed minimal disease elderly 60 – 80 y males (CSHA 3) and light blue

bars denote vulnerable elderly 60 – 80 y males (CSHA 4). Asterisks denote statistically significant differences in

categories, with a p-value <0.05.

Fig. 2 Transverse sections of proximal right leg muscles (A) and distal

right muscles (B) with colour differentiation of individual muscles (red: left

quadriceps mass; green: right quadriceps mass; dark blue: hamstrings,

light blue: rectus femoris; pink: peroneal and tibialis anterior muscles;

yellow: gastrocnemius)

*

Fig. 3 Canadian Study of Health and

Ageing (CSHA) scoring of frailty. CSHA

categories 1 – 4 were selected in this study

to identify the early markers of frailty in

mobile and physically active elderly.