The utility of a portable muscle ultrasound in the assessment of muscle alterations in children with acute lymphoblastic leukaemia

BACKGROUND During treatment for acute lymphoblastic leukaemia (ALL), children are prone to musculoskeletal deterioration. However, non-invasive tools to measure muscle mass and intramuscular alterations are limited. In this study we explored the feasibility of muscle ultrasound in children with ALL. Additionally, we analysed whether automated ultrasound outcomes of muscle size and intramuscular fat infiltration (IMAT) were associated with appendicular skeletal muscle mass (ASMM), muscle strength and physical performance. METHODS Children with ALL, aged 3-18 years were included during maintenance therapy. Bilateral images of the rectus femoris muscle were captured using a portable linear array transducer connected to a tablet. Subsequently, an automated image annotation software (MuscleSound) was used to estimate cross-sectional area, muscle thickness and IMAT. Feasibility was assessed using acceptance (percentage of children approached who were enrolled), practicality (percentage of children that completed the ultrasound measurement after enrolment) and implementation (percentage of children that had sufficient imaging to be processed and analysed by the software). Assessments of ASMM by bioimpedance analysis, muscle strength using handheld dynamometry and timed physical performance tests were administered at the same visit. Multivariable linear models were estimated to study the associations between muscle ultrasound outcomes and ASMM, strength and physical performance, adjusted for sex, age, body mass index and ALL treatment week. RESULTS Muscle ultrasound was performed in 60 out of 73 invited patients (76.9%), of which 37 were boys (61.7%), and median age was 6.1 years (range: 3-18.8 years). The acceptance was 98.7%, practicality 77.9% and implementation was 100%. Patients who refused the examination (n = 13) were younger (median: 3.6, range: 3-11.2 years) compared with the 60 examined children (P = 0.0009). In multivariable models, cross-sectional area was associated with ASMM (β = 0.49 Z-score, 95% confidence interval [CI]:0.3,2.4), knee-extension strength (β = 16.9 Newton [N], 95% CI: 4.8, 28.9), walking performance (β = -0.46 s, 95% CI: -0.75, -0.18) and rising from the floor (β = -1.07 s, 95% CI: -1.71, -0.42). Muscle thickness was associated with ASMM (β = 0.14 Z-score, 95% CI: 0.04, 0.24), knee-extension strength (β = 4.73 N, 95% CI: 0.99, 8.47), walking performance (β = -0.13 s, 95% CI: -0.22, -0.04) and rising from the floor (β = -0.28 s, 95% CI: -0.48, -0.08). IMAT was associated with knee-extension strength (β = -6.84 N, 95% CI: -12.26, -1.41), walking performance (β = 0.2 s, 95% CI: 0.08, 0.32) and rising from the floor (β = 0.54 s, 95% CI: 0.27, 0.8). None of the muscle ultrasound outcomes was associated with handgrip strength. CONCLUSIONS Portable muscle ultrasound appears a feasible and useful tool to measure muscle size and intramuscular alterations in children with ALL. Validation studies using magnetic resonance imaging (gold standard) are necessary to confirm accuracy in paediatric populations.

[1]  A. Alonso-Martínez,et al.  Associations between physical fitness components with muscle ultrasound parameters in prepuberal children , 2022, International Journal of Obesity.

[2]  F. Diefenthaeler,et al.  Influence of subcutaneous adipose thickness and dominance on reliability of quadriceps muscle quality in healthy young individuals , 2021, Journal of Ultrasound.

[3]  R. Pieters,et al.  Dexamethasone-Induced Sarcopenia and Physical Frailty in Children With Acute Lymphoblastic Leukemia: Protocol for a Prospective Cohort Study , 2021, JMIR research protocols.

[4]  R. Makuch,et al.  Test–Retest Reliability of Handgrip Strength Measurement in Children and Preadolescents , 2020, International journal of environmental research and public health.

[5]  A. Pastva,et al.  Novel approaches to metabolic assessment and structured exercise to promote recovery in ICU survivors. , 2020, Current opinion in critical care.

[6]  J. Calleja-González,et al.  Indirect Assessment of Skeletal Muscle Glycogen Content in Professional Soccer Players before and after a Match through a Non-Invasive Ultrasound Technology , 2020, Nutrients.

[7]  S. Heymsfield,et al.  Low muscle mass and strength in pediatrics patients: Why should we care? , 2019, Clinical nutrition.

[8]  T. Lohman,et al.  Relative Body Weight and Standardised Brightness-Mode Ultrasound Measurement of Subcutaneous Fat in Athletes: An International Multicentre Reliability Study, Under the Auspices of the IOC Medical Commission , 2019, Sports Medicine.

[9]  B. Nicklas,et al.  Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study , 2019, Cardio-Oncology.

[10]  René Rizzoli,et al.  Sarcopenia: revised European consensus on definition and diagnosis , 2018, Age and ageing.

[11]  L. Andersen,et al.  Testing physical function in children undergoing intense cancer treatment—a RESPECT feasibility study , 2018, Pediatric blood & cancer.

[12]  Kunihiko Kobayashi,et al.  Sarcopenia after induction therapy in childhood acute lymphoblastic leukemia: its clinical significance , 2018, International Journal of Hematology.

[13]  M. Leow,et al.  Skeletal Muscle Ultrasonography in Nutrition and Functional Outcome Assessment of Critically Ill Children: Experience and Insights From Pediatric Disease and Adult Critical Care Studies , 2017, JPEN - Journal of Parenteral and Enteral Nutrition.

[14]  R. Barr,et al.  Importance of Nutrition in the Treatment of Leukemia in Children and Adolescents. , 2016, Archives of medical research.

[15]  S. Mathur,et al.  Muscle analysis using pQCT, DXA and MRI. , 2016, European journal of radiology.

[16]  P. Wischmeyer,et al.  Winning the war against ICU-acquired weakness: new innovations in nutrition and exercise physiology , 2015, Critical Care.

[17]  Qun Zhao,et al.  Measurement of intramuscular fat by muscle echo intensity , 2015, Muscle & nerve.

[18]  M. Ribeiro,et al.  Timed motor function tests capacity in healthy children , 2015, Archives of Disease in Childhood.

[19]  D. Hernandez,et al.  Reliability, Validity, and Diagnostic Value of a Pediatric Bioelectrical Impedance Analysis Scale. , 2015, Childhood obesity.

[20]  Kevin A Zwetsloot,et al.  Ultrasonic assessment of exercise-induced change in skeletal muscle glycogen content , 2015, BMC Sports Science, Medicine and Rehabilitation.

[21]  P. Nathan,et al.  Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia , 2015, Leukemia & lymphoma.

[22]  R. Pieters,et al.  The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia , 2015, Haematologica.

[23]  Marco Paoloni,et al.  Clinical definition of sarcopenia. , 2014, Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases.

[24]  S. Jebb,et al.  Skeletal muscle mass reference curves for children and adolescents , 2014, Pediatric obesity.

[25]  R. Barr,et al.  Age- and gender-dependent values of skeletal muscle mass in healthy children and adolescents , 2011, Journal of cachexia, sarcopenia and muscle.

[26]  T. Takken,et al.  Is grip strength a predictor for total muscle strength in healthy children, adolescents, and young adults? , 2010, European Journal of Pediatrics.

[27]  Maria E Fernandez,et al.  How we design feasibility studies. , 2009, American journal of preventive medicine.

[28]  F. Gabreëls,et al.  Validity and reproducibility of the Jamar dynamometer in children aged 4 – 11 years , 2006, Disability and rehabilitation.

[29]  Mary P Galea,et al.  Investigation of the timed‘Up & Go’test in children , 2005, Developmental medicine and child neurology.

[30]  B. Lange,et al.  Strength and functional mobility in children with acute lymphoblastic leukemia. , 2003, Medical and pediatric oncology.

[31]  J M Wit,et al.  Body index measurements in 1996–7 compared with 1980 , 2000, Archives of disease in childhood.

[32]  D. Silva,et al.  Body composition estimation in children and adolescents by bioelectrical impedance analysis: A systematic review. , 2018, Journal of bodywork and movement therapies.

[33]  A. Brinksma Nutritional status in children with cancer: Prevalence, related factors, and consequences of malnutrition , 2014 .

[34]  Stef van Buuren,et al.  Continuing Positive Secular Growth Change in the Netherlands 1955–1997 , 2000, Pediatric Research.