Radiological Assessment of Sarcopenia and Its Clinical Impact in Patients with Hepatobiliary, Pancreatic, and Gastrointestinal Diseases: A Comprehensive Review

Abstract Sarcopenia is defined as a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life, and death. The diagnosis of sarcopenia is based on documentation of two of the three criteria: low muscle mass, low muscle strength, and low physical performance. Imaging-based assessment of muscle mass is preferred in both clinical and research settings. Anthropometry for the evaluation of muscle mass is prone to errors and is not recommended in the clinical setting. There is a lack of literature on the radiological assessment of sarcopenia and its association with prognosis in hepatobiliary, pancreatic, and gastrointestinal diseases. Thus, we aim to provide a review of studies that utilized radiological methods to assess sarcopenia and evaluate its impact on outcomes in patients with these diseases.


Introduction
Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life, and death. 1 Sarcopenia can be classified as primary and secondary according to the age at onset and associated inciting factors.Aging has been classically associated with primary sarcopenia, whereas secondary sarcopenia can result in any age group and is related to the underlying disease process. 2 Due to its increased relevance in determining outcomes in the geriatric population, cancer patients, and patients with chronic illness, sarcopenia is recognized as a disease entity in the International Classification of Diseases Tenth Revision (ICD-10). 3The sarcopenia disease burden is expected to increase to around 200 million by the end of sarcopenia, and radiological investigations have become increasingly important.Dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), and magnetic resonance imaging (MRI) are most widely used for the assessment of sarcopenia.Various parameters and criteria have been used to diagnose sarcopenia. 7lthough, readily available, ultrasound is not reproducible and no widely accepted consensus is available for cut-off values of sarcopenia.
DEXA is readily available, cost-effective, and reproducible.It is a widely accepted modality for sarcopenia assessment.The lean mass derived from DEXA scan can be used to calculate the appendicular skeletal mass index (ASMI), which is a measure of sarcopenia on DEXA.
CT is considered the gold standard for body composition analysis and is used as a screening tool for assessment of sarcopenia (►Table 1).Skeletal muscle index (SMI) is the most commonly used parameter for sarcopenia.It is calculated at the level of L3 or L4 on a CT scan by segmentation (►Fig. 1). 1 Peripheral quantitative CT (pQCT) is a novel imaging modality primarily used to investigate bone mineral content.pQCT produces a cross-sectional image that enables quantification of three-dimensional tissue structure and skeletal muscle evaluation.It has extremely low radiation exposure and short scan time with relatively lower cost; however, it lacks standardization.The limitations of CT are exposure to ionizing radiation and inability to distinguish between intra-myocellular fat and intermuscular fat.
MRI can assess muscle composition by using several semiquantitative or quantitative sequences without the need of ionizing radiation.Muscle quality abnormalities, such as muscle disruption, edema, myosteatosis, and myofibrosis can also be evaluated on MRI (►Fig.2).T2 mapping, magnetic resonance spectroscopy, Dixon sequence, diffusion tensor imaging, and strain rate tensor imaging can be used for assessment of sarcopenia. 4 Though MRI can differentiate between intra-myocellular fat and intermuscular fat (which was a drawback of CT), it is costly and time-consuming and there are no specific cut-offs for diagnosis of sarcopenia.
Sarcopenia is frequently detected in patients with hepatobiliary, gastrointestinal, and pancreatic disorders and has been associated with decreased overall survival (OS), a higher mortality rate, hospitalization, and postoperative complications.Because these patients frequently undergo imaging for diagnosis or follow-up, radiological tests can effectively assess sarcopenia in this group of patients.This review aims to review studies that utilized radiological methods for assessing sarcopenia and evaluate its impact on outcomes in patients with hepatobiliary, pancreatic, and gastrointestinal diseases.
We systematically reviewed the PUBMED database with the search terms "sarcopenia" AND "imaging."Studies were eligible for inclusion if they evaluated the impact of sarcopenia diagnosed by imaging in hepatobiliary, pancreatic, and gastrointestinal systems.Exclusion criteria included case series (<10 patients), case reports, letters to editors, reviews, meta-analysis, pediatric studies (age < 12 years), studies that evaluated sarcopenia clinically without utilizing radiological tests, and those with insufficient data.We collected data from the selected studies regarding patient demographics, type of study, the origin of the study population, the Abbreviations: CT, computed tomography; SMI, skeletal muscle index.
Fig. 1 Computed tomography (CT) image of a 50-year-old male who had vague abdominal pain.Image depicts utilization of segmentation technique in CT for calculating skeletal mass index at L3 level.In this case, the skeletal mass index was 60 cm 2 /m 2 (>52.4 cm 2 / m 2 cut-off), suggesting that there is no sarcopenia.
radiological method used for sarcopenia detection, measurement techniques, muscle site, area, and cut-off values.In addition, predictive outcomes and complications related to the prevalence and degree of sarcopenia in these diseases were recorded.

Radiological Assessment of Sarcopenia
Our literature search yielded 305 studies.After filtering out duplicates and screening titles and abstracts, 136 studies met the inclusion criteria.  ►Tab 2 enumerates all these studies.These studies were published from 2012 to 2022.The total number of subjects/patients evaluated in these studies was 33,960.Abdominal CT was the most common imaging modality in these studies.The most common measurement parameter used for the measurement of sarcopenia in CT and MRI was SMI in 80 (58.8%) studies.The other commonly used parameters included psoas muscle area, transverse psoas muscle thickness (TPMT), and total abdominal muscle areas, which were used in 10, 4, and 3 studies, respectively.In MRI, sarcopenia was estimated using fat-free muscle areas, while in DEXA, ASMI was utilized.In addition to muscle area quantification, some of the studies used mean muscle attenuation values (n ¼ 14) or intramuscular adipose content (n ¼ 6) for qualitative assessment of myosteatosis.Most of these studies utilized L3 levels for the measurement of sarcopenia.
These studies' cut-off criteria for diagnosing sarcopenia showed marked heterogeneity with 24 different genderspecific cut-off values for SMI.The most common cut-off value for SMI was less than 52.4 cm 2 /m 2 in males and less than 38.5 cm 2 /m 2 in females.Few studies also employed cut-off values based on body mass index.Some studies relied on a change in SMI measurement on serial imaging.For assessment of myosteatosis, average muscle attenuation cut-off values varied from 31.4 to 41 HU.

Sarcopenia and Chronic Liver Disease
Eleven studies analyzed the impact of sarcopenia on clinical outcomes in patients with chronic liver disease (CLD; ►Table 3). 17,63,66,67,71,88,90,93,100,125,128here were 2,789 patients (aged 54 to 68.4 years).Most studies were retrospective.Two studies also recruited a control group. 67,90Abdominal CT was the commonest modality used (nine studies).The commonest parameters were SMI and TPMT.In addition, one of these studies evaluated the relationship between sarcopenia and response after transjugular intrahepatic portosystemic shunts, 90 while two other studies compared sarcopenia with biochemical markers of cirrhosis. 71,125Overall, these studies showed that sarcopenia has a negative impact on survival and is associated with the development of acute decompensation.

Sarcopenia and Hepatocellular Carcinoma
Cancer is associated with reduced fat and muscle stores with resultant wasting and cachexia in later stages.The prevalence of sarcopenia in patients with CLD and hepatocellular carcinoma (HCC) is higher (►Table 4).
Sarcopenia in this group of patients is associated with negative impact on outcomes.There were 34 studies (7,836 patients, age 53.9 to 73 years) reporting radiological assessment of sarcopenia and its prognostic impact in CLD patients with HCC. 10,15,16,18  Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.  121,123,129,131,133,137 There were 32 retrospective and 2 prospective studies.The studies included both newly diagnosed and advanced HCCs.Twelve studies included patients with HCC who underwent hepatectomy or transplant.In six studies, patients were on systemic chemotherapy or immunotherapy 53,56,68,111,129,133 and in another seven studies, patients underwent locoregional therapies. 10,21,61,109,119,123,137The most common modality was CT (n ¼ 33), and the commonest parameter was SMI.Most studies reported poor outcomes including OS and HCC recurrence in patients with sarcopenia.

Sarcopenia and Liver Transplant
,60,70,78,84,87,94,96,97,113,120,133,138,139 Two studies included patients who underwent emergent liver transplant following acute liver failure. 87,139SMI was the most common parameter.Sarcopenia was associated with increased mortality, graft failure, reduced OS, and increased postoperative complications and infections in these studies, except for the study by Dhaliwal et al, 96 in which there was no difference in clinical outcomes between sarcopenic and nonsarcopenic patients.A study by van Vugt et al showed that sarcopenia is associated with increased health care costs and longer hospital stay following transplantation. 70

Sarcopenia and Inflammatory Bowel Disease
Studies predominantly assessed the relationship of sarcopenia with adverse outcomes and postoperative complications in patients with inflammatory bowel disease.There were 16 studies (1,589 patients, age 17.9 to 43.8 years). 27,29,30,35,38,44,46,47,69,79,95,99,110,115,118,135Ten studies specifically were related to Crohn's disease (►Table 6).One study assessed the feasibility of MRI for the detection of skeletal muscle mass. 95In contrast, the rest of the studies evaluated the association of sarcopenia with adverse outcomes such as the need for surgery, increased hospitalization, abscesses, and fistula formation.CT was the commonest imaging modality used, and SMI was the parameter employed for the assessment of sarcopenia and muscle mass.

Sarcopenia and Biliary, Pancreatic, Gastrointestinal, and Colorectal Malignancy
Association between cancer and muscle function has been increasingly evaluated over the last decade.There is an association between sarcopenia with mortality, OS,       Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.
Six studies compared outcomes of sarcopenia in these malignancies following chemotherapy. 76,91,124,126,127,144ost studies also report the effect of sarcopenia on postoperative complications and OS in these patients who had undergone surgical resection of malignancy.One study had reported the influence of sarcopenia and muscle mass on the development of pancreatic fistula formation in patients following pancreatoduodenectomy. 32A study by van Vugt et al showed that sarcopenia is associated with increased health care costs in patients with malignancy of the alimentary tract. 51

Sarcopenia and Pancreatitis
Ten studies evaluated the radiological detection of sarcopenia in patients with pancreatitis (chronic pancreatitis in eight and acute pancreatitis in two). 49,50,54,55 75,82,103,107,112,116 f these studies, two studies evaluated outcomes in chronic pancreatitis patients undergoing total pancreatectomy with auto islet transplantation 103,107 (►Table 9).

Expert Opinion and Future Directions
Sarcopenia is gaining importance as a prognostic marker of several diseases.In the context of hepatobiliary, pancreatic, and gastrointestinal disorders, more than 100 studies have reported the negative impact of sarcopenia assessed at radiological investigations on clinical outcomes.Radiological assessment is preferred to evaluate skeletal muscle mass, a key component of sarcopenia.Anthropometry-based evaluation of muscle mass is unreliable.CT is the most common radiological modality utilized for assessing sarcopenia as it is widely available.Most patients with hepatobiliary, pancreatic, and gastrointestinal diseases undergo CT as a part of their evaluation.Various parameters are used to evaluate sarcopenia at CT. Several cut-off values have been proposed.Due to this variability, as well as the need for manual measurements, the utilization of imaging for the clinical assessment of sarcopenia is hampered.Therefore, till recently, radiological assessment of sarcopenia has been used in the research setting only.Standardizing radiological methods and the cut-off for assessing sarcopenia is necessary.Automating measurements will significantly help allow the seamless incorporation of imaging in the clinical assessment of sarcopenia.Artificial intelligence can be utilized to achieve this.Finally, in the future, indices that account for both obesity and sarcopenia may be developed, and these may fully explore the impact of body composition on the outcomes.

Author Contribution
S.F.: data curation, writing-original draft preparation; S. S.: data curation, writing-original draft preparation; A. Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.

Fig. 2
Fig. 2 Dixon MRI sequence of the right thigh in a 64-year-old woman.Axial T1W in-phase (a), out of-phase (b), 100% fat images (c), and 100% water images (d) are shown.The images depict reduction in the muscle bulk with fatty infiltration of the muscles (as seen by chemical shift artefact on out-of-phase image).These findings are suggestive of myosteatosis and sarcopenia.MRI, magnetic resonance imaging.

Table 1
Sarcopenia measurement at CT

Table 2
Diagnostic modalities, measurement methods, and cut-off values for diagnosing sarcopenia

Table 2 (
Continued)Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.
Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).

Table 4
Studies reporting association of sarcopenia with outcomes in patients with hepatocellular carcinoma Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.

Table 4 (
Continued) Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.

Table 4 (
Continued) Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.

Table 4 (
Continued) Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.

Table 5
Studies reporting association of sarcopenia with outcomes in liver transplant patients Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).

Table 7
Studies reporting association of sarcopenia with outcomes in biliary and pancreatic malignancy Author Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).

Table 7 (
Continued) a Median, rest mean Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.

Table 8
Studies reporting association of sarcopenia with outcomes in gastrointestinal/colorectal malignancies Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.

Table 8 (
Continued)Radiological Assessment of Sarcopenia and Its Clinical Impact Farook et al.
Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).
Abbreviationsa Mean age.b Studies which showed no significant correlation between sarcopenia and clinical outcome.Journal of Gastrointestinal and Abdominal Radiology ISGAR © 2023.The Author(s).

Table 9
Studies reporting association of sarcopenia with outcomes in pancreatitis