Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. to CT for surveillance of treated TETs, although if there is insurmountable susceptibility artifact from sternotomy wires using fast spin-echo and other MRI techniques, alternating MRI and CT follow-up can be performed [100].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Cross-sectional imaging by MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft- tissue contrast [48-52]. As a supplement to static assessment of tissue plane transgression, dynamic MRI [45-48] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures, confirm or exclude adherence of the mass to adjacent structures, and observe diaphragmatic motion in real time [80-84]; paradoxical motion or lack of motion can indicate phrenic nerve involvement by the mediastinal mass, without the need to perform a subsequent fluoroscopic sniff test.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. US Chest There is little relevant literature to support US of an indeterminate mediastinal mass on FDG-PET/CT. Transthoracic US can be used to evaluate mediastinal masses when accessible to the sonographic window, delineating their size, location, cystic versus solid nature, relationship to important vascular structures, and vascularity, with some diagnostic potential [89]. Endoscopic US can similarly evaluate mediastinal masses when encompassed in the sonographic window [90]. The tissue characterization capability of US is inferior to MRI but not to CT.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Image-Guided Transthoracic Needle Biopsy CT-guided percutaneous needle and core biopsy of accessible mediastinal masses has been shown to be safe and to have a good diagnostic yield, with core biopsy more effective than fine-needle aspiration. Biopsy was more frequently diagnostic for TETs than for lymphoma [101-104]. A retrospective study of 293 consecutive CT-guided mediastinal biopsies performed in 285 patients showed an overall diagnostic yield of 87% for mediastinal masses with a mean size of 5.3 cm and 57% for residual masses at the site of treated lymphoma [101]. Another retrospective study of 52 patients reported a 77% diagnostic yield for needle biopsy of mediastinal masses with a mean size of 6.9 cm [102]. When the distinction of TETs from lymphoma cannot be definitively made by imaging, image-guided biopsy has a role. PET/CT guidance for biopsy reportedly yields no diagnostic advantage [104]. When the lesion is visible within the sonographic window, transthoracic US-guided biopsy of mediastinal masses is also feasible, with color Doppler and contrast-enhanced sonographic techniques providing additional value [105-108], and with core biopsy more effective than fine-needle aspiration. Endoscopic biopsy of mediastinal masses is also feasible and effective, although not in the purview of this topic [109]. DWI MR may be helpful in directing CT-guided biopsy toward sites of higher cellularity and diagnostic yield [110], as may DCE MRI with postprocessed subtraction. MR- guided percutaneous needle biopsy has also been shown to be safe and diagnostically accurate [111].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Radiography Chest After cross-sectional imaging has been performed for mediastinal mass evaluation, there is seldom a role for chest radiography.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. FDG-PET/CT Skull Base to Mid-Thigh Unless the degree of metabolic activity of a mediastinal mass is sought and deemed capable of changing clinical management, FDG-PET/CT would be unlikely to add diagnostic information regarding a mediastinal mass beyond that offered by MRI. FDG-PET/CT offers limited additional value beyond that of conventional CT and MRI in the assessment of mediastinal masses [53], with the exception of its use for primary mediastinal lymphoma staging and surveillance and detection of metastatic lymphadenopathy, the latter of which is not within the scope of this topic. FDG-PET/CT has become the standard for staging and assessment of treatment response for lymphomas that are FDG-PET-avid at baseline or at the time recurrence [91-97]. A caveat is that although a negative surveillance FDG- PET/CT is reassuring of a good outcome, a positive FDG-PET/CT can be misleading, as it does not always implicate


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Imaging of Mediastinal Masses residual or recurrent lymphoma [96,98]. With regard to prevascular mediastinal masses, a negative FDG-PET/CT has been shown to be helpful in excluding malignancy; however, a positive FDG-PET/CT has little value for discrimination between benign and malignant lesions [53]. The frequent FDG-PET/CT avidity of normal and hyperplastic thymus [54] is a confounder in FDG-PET/CT assessment of the prevascular mediastinum. Benign thymic cysts can also be FDG-PET/CT-avid [42]. Combined use of FDG-PET/CT and DCE MRI has been shown to be helpful to distinguish prevascular mediastinal solid tumors from one another [55]. Higher SUVs on FDG- PET/CT are more frequently found in high-risk thymoma, thymic carcinoma, and lymphoma than in low-risk thymoma [55-57]. FDG-PET/CT appears to be more sensitive than CT alone for detection of mediastinal recurrence of thymoma [99].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Cross-sectional imaging by MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft- tissue contrast [48-52]. As a supplement to static assessment of tissue plane transgression, dynamic MRI [45-48] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures, to confirm or exclude adherence of the mass to adjacent structures, and to observe diaphragmatic motion in real time [80-84]; paradoxical motion or lack of motion can indicate phrenic nerve involvement by the mediastinal mass, without the need to perform a subsequent fluoroscopic sniff test.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. US Chest Transthoracic US is unlikely to offer additional information regarding mediastinal mass characterization beyond that of MRI.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Image-Guided Transthoracic Needle Biopsy CT-guided percutaneous needle and core biopsy of accessible mediastinal masses has been shown to be safe and to have a good diagnostic yield, with core biopsy more effective than fine-needle aspiration. Biopsy was more frequently diagnostic for TETs than for lymphoma [101-104]. A retrospective study of 293 consecutive CT-guided mediastinal biopsies performed in 285 patients showed an overall diagnostic yield of 87% for mediastinal masses with a mean size of 5.3 cm and 57% for residual masses at the site of treated lymphoma [101]. Another retrospective study of 52 patients reported a 77% diagnostic yield for needle biopsy of mediastinal masses with a mean size of 6.9 cm [102]. When the distinction of TETs from lymphoma cannot be definitively made by imaging, image-guided


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Imaging of Mediastinal Masses


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. biopsy has a role. PET/CT guidance for biopsy reportedly yields no diagnostic advantage [104]. When the lesion is visible within the sonographic window, transthoracic US-guided biopsy of mediastinal masses is also feasible, with color Doppler and contrast-enhanced sonographic techniques providing additional value [105-108], and with core biopsy more effective than fine-needle aspiration. Endoscopic biopsy of mediastinal masses is also feasible and effective, although not in the purview of this topic [109]. DWI MR may be helpful in directing CT-guided biopsy toward sites of higher cellularity and diagnostic yield [110], as may DCE MRI with postprocessed subtraction. MR- guided percutaneous needle biopsy has also been shown to be safe and diagnostically accurate [111].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses


Breast Pain

Breast Pain. Introduction/Background Breast pain is a common complaint for which patients seek medical attention, with a prevalence of up to 70% to 80% [1-5]. However, breast pain or tenderness is rarely found to result from cancer when not associated with a palpable mass or other suspicious clinical finding. Studies show that the incidence of breast cancer in patients with breast pain as their only symptom is 0% to 3.0% [6-13]. Some authors have found no increased risk of malignancy in patients with breast pain, while others have even found a decreased risk when compared to those without pain [14,15].


Breast Pain

Breast Pain. Breast pain should be triaged into one of two categories: pain that is not suspicious for associated malignancy versus pain that may be clinically significant. Clinically insignificant pain is cyclical (temporally associated with the menstrual cycle) or nonfocal/diffuse, either unilateral or bilateral. This type of pain is not associated with malignancy [8]. Benign causes of breast pain are numerous and include hormonal variations, larger cup size, ill- fitting or unsupportive bra, lower levels of fitness or activity, fibromyalgia, cysts, periductal mastitis, stretching of Cooper ligaments, fat necrosis, surgery, Mondor disease, diabetic mastopathy, duct ectasia, musculoskeletal disease, referred nerve root pain from degenerative spinal changes, herpes zoster, heart disease, biliary pain, and peptic ulcer [3,5,16-26].


Breast Pain

Breast Pain. Clinically significant pain, while still overwhelmingly due to a benign etiology, has occasionally been found to be associated with malignancy [8,9,11,12]. When malignancy related, pain tends to be well localized and persistent [27]. Therefore, breast pain is considered potentially clinically significant when it persists and is focal, defined as involving <25% of the breast and axillary tissue.


Breast Pain

Breast Pain. Special Imaging C onsiderations Special Imaging Considerations Digital breast tomosynthesis (DBT) can address some of the limitations encountered with standard mammographic views. In addition to planar images, DBT allows for creation and viewing of thin-section reconstructed images that may decrease the lesion-masking effect of overlapping normal tissue, and reveal the true nature of potential false positive findings without the need for recall. While there is no specific literature assessing its use in evaluation of breast pain, DBT can be useful in the diagnostic setting, improving lesion characterization [28-31] in noncalcified lesions, when compared to conventional mammographic workup.


Breast Pain

Breast Pain. The following discussion is for cases of isolated breast pain without other symptoms. In cases where the pain is associated with other symptoms, for example, lump or nipple discharge, pain should be considered a secondary symptom and the workup should follow the ACR Appropriateness Criteria recommendations for that additional symptom.


Breast Pain

Breast Pain. aEmory University Hospital, Atlanta, Georgia. bPanel Vice-Chair, NYU Clinical Cancer Center, New York, New York. cGeorge Washington University Hospital, Washington, District of Columbia. dRoper St. Francis Physician Partners Breast Surgery, Charleston, South Carolina; American College of Surgeons. eNorthwestern University Feinberg School of Medicine, Chicago, Illinois; American College of Physicians. fNew York University School of Medicine, New York, New York. gThe University of Texas MD Anderson Cancer Center, Houston, Texas. hNew York University School of Medicine, New York, New York. iAlpert Medical School of Brown University, Providence, Rhode Island. jBeth Israel Deaconess Medical Center, Boston, Massachusetts. kH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. lBeth Israel Deaconess Medical Center, Boston, Massachusetts. mWomen and Infants Hospital, Providence, Rhode Island; American Congress of Obstetricians and Gynecologists. nMecklenburg Radiology Associates, Charlotte, North Carolina. oDonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York. pPerelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania. qPanel Chair, Emory University Hospital, Atlanta, Georgia.


Breast Pain

Breast Pain. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document.


Breast Pain

Breast Pain. Reprint requests to: publications@acr.org


Breast Pain

Breast Pain

Breast Pain. Breast Pain


Breast Pain

Breast Pain. Discussion of Procedures by Variant Discussion of Procedures by Variant Variant 1: Female with clinically insignificant breast pain (nonfocal [greater than one quadrant], diffuse, or cyclical) without other suspicious clinical finding. Any age. Initial imaging. Mammography There is very limited literature specifically evaluating the use of imaging in patients with nonfocal or cyclical breast pain. In a retrospective review of 236 patients with breast pain, authors found no mammographic or sonographic correlate in the 10 patients who had cyclical breast pain [8].


Breast Pain

Breast Pain. Given that this type of breast pain is not associated with malignancy, the use of mammography beyond the usual screening recommendations is not expected to result in increased cancer detection. Some argue that imaging may be helpful in order to reassure the patient of the absence of malignancy [14,32]. One study found patients with breast pain reported a decreased level of pain and anxiety after sonography [33]. However, the assumption that negative imaging reassures the patient or clinician is challenged by a retrospective cohort study that found that imaging women with breast pain at the time of the initial clinical visit increased the odds of subsequent clinical visits [34].


Breast Pain

Breast Pain. DBT DBT There is no relevant literature regarding the specific use of DBT in the evaluation of nonfocal or cyclical breast pain.


Breast Pain

Breast Pain. US Breast There is scant literature specifically evaluating the use of ultrasound (US) imaging in patients with nonfocal or cyclical breast pain. In a retrospective review of 236 patients with breast pain, authors found no mammographic or sonographic correlate in the 10 patients who had cyclical breast pain [8]. A prospective study of 76 patients younger than age 30 who presented with cyclical breast pain as their only complaint and underwent US found no malignancy [35]. A limitation of this study was the lack of follow-up.


Breast Pain

Breast Pain. MRI Breast There is no relevant literature regarding the use of MRI in the evaluation of nonfocal or cyclical breast pain.


Breast Pain

Breast Pain. Sestamibi MBI There is no relevant literature regarding the use of molecular breast imaging (MBI) in the evaluation of nonfocal or cyclical breast pain.


Breast Pain

Breast Pain. Variant 2: Female with clinically significant breast pain (focal and noncyclical). Age less than 30. Initial imaging. Mammography There is little in the literature specifically evaluating the use of mammography in patients less than 30 years of age who have focal and noncyclical breast pain. Because of greater breast density, mammography is known to be less accurate than US in evaluating symptomatic women less than 30 years of age [36].


Breast Pain

Breast Pain. DBT DBT There is no relevant literature regarding the use of DBT in the evaluation of focal and noncyclical breast pain in patients less than 30 years of age.


Breast Pain

Breast Pain. US Breast US Breast The literature regarding the efficacy of US in evaluation of breast pain is somewhat limited by lack of age-group- specific results. Most authors have found that cancer is a rare cause of focal, clinically significant breast pain [12,35], and that US has a high negative predictive value (NPV), sensitivity, and specificity for evaluation of breast pain. Leddy et al [11] performed a retrospective review of 257 patients who underwent US after presenting with focal breast pain and found cancer in 1.2% of patients, with a sensitivity of 100%, specificity of 92.5%, positive predictive value of 13.6%, and NPV of 100%. Loving et al [37] found a 100% NPV and sensitivity in their retrospective study of 830 patients less than 30 years of age with focal breast signs or symptoms (not limited to but including breast pain).


Breast Pain

Breast Pain. Some authors suggest that, despite the low incidence of malignancy, US may be useful in that it could potentially find treatable causes of breast pain, such as cysts [9]. On the other hand, a prospective, observational follow-up study of 987 patients with breast pain alone found benign findings in 8.6% of cases, which consisted mostly of


Breast Pain

Breast Pain. small cysts [14]. The authors argued that in the absence of a palpable abnormality, any cyst that may be found by US would be unlikely to be large enough to cause pain or benefit from aspiration.


Breast Pain

Breast Pain. MRI Breast There is no relevant literature regarding the use of MRI in the evaluation of focal and noncyclical breast pain.


Breast Pain

Breast Pain. Sestamibi MBI There is no relevant literature regarding the use of MBI in the evaluation of focal and noncyclical breast pain.


Breast Pain

Breast Pain. Variant 3: Female with clinically significant breast pain (focal and noncyclical). Age 30 to 39. Initial imaging. Mammography Though the incidence is low, mammography may be used to exclude malignancy in cases of focal and noncyclical breast pain. Mammography was found to have a high sensitivity (100%) and NPV (100%) in a retrospective review of 206 patients with focal breast pain [11]. While this study found specificity to be slightly lower at 87.6%, another retrospective study of focal, noncyclical pain calculated a specificity of mammography of 97% for nondense breasts and 96% for dense breasts [9]. Additionally, Tumyan et al [38] in a retrospective study of mammography in combination with US found a NPV of 100%, though the study was limited by a significant number of patients being lost to follow-up.


Breast Pain

Breast Pain. DBT DBT While there is no literature specifically evaluating the use of DBT in the workup of focal and noncyclical breast pain, DBT can be useful in the diagnostic setting. It is known to improve lesion characterization in noncalcified lesions and cancer detection when compared to conventional mammographic workup [28-30,39-41].


Breast Pain

Breast Pain. US Breast While there are few studies evaluating US independently of mammography in the setting of focal and noncyclical breast pain, the existing literature suggests that US may be useful to exclude malignancy in these cases. A retrospective review of 110 cases of focal breast pain evaluated by US found no imaging abnormality in 85 cases (77.3%) [12] and there were no malignancies. In 15 cases (13.6%), cysts were identified, and 3 patients (2.7%) had solid masses, all of which were benign. Fluid collections and edema were seen in the remaining cases.


Breast Pain

Breast Pain. Several studies have evaluated the usefulness of US in addition to mammography in cases of focal, noncyclical breast pain and concluded that in the setting of a negative mammogram, US may not be indicated, especially in patients with nondense breasts. A retrospective study of 206 patients with focal breast pain as their only symptom evaluated with US after a mammogram found that US resulted in 8 additional biopsies and 14 additional 6-month follow-up examinations without detecting any additional cancers [11]. Another retrospective study found 76 imaging abnormalities in 413 cases of focal pain, with 46 (61%) seen on US alone, for a specificity of 82%. While there were no malignancies, US found a benign lesion in 40 of 56 cases in which mammography was negative in patients with dense breasts and found a benign lesion in 6 of 20 cases with a negative mammogram and nondense breasts. The specificity of US was 95% for nondense breasts and 87% for dense breasts [9].


Breast Pain

Breast Pain. Some authors suggest that, despite the low incidence of malignancy, US may be useful in that it could potentially find treatable causes of breast pain, such as cysts [9]. On the other hand, a prospective, observational follow-up study of 987 patients with breast pain alone found benign findings in 8.6% of cases, which consisted mostly of small cysts [14]. The authors argued that in the absence of a palpable abnormality, any cyst that may be found by US would be unlikely to be large enough to cause pain or benefit from aspiration.


Breast Pain

Breast Pain. MRI Breast MRI Breast There is no relevant literature regarding the use of MRI in the evaluation of focal and noncyclical breast pain.


Breast Pain

Breast Pain. Sestamibi MBI Sestamibi MBI There is no relevant literature regarding the use of MBI in the evaluation of focal and noncyclical breast pain.


Breast Pain

Breast Pain. Variant 4: Female with clinically significant breast pain (focal and noncyclical). Age greater than or equal to 40. Initial imaging.


Breast Pain

Breast Pain. Mammography Though the incidence is low, mammography may be used to exclude malignancy in cases of focal and noncyclical breast pain. Mammography was found to have a high sensitivity (100%) and NPV (100%) in a retrospective review of 206 patients with focal breast pain [11]. While this study found specificity to be slightly lower at


Breast Pain

Breast Pain

Breast Pain. Breast Pain


Breast Pain

Breast Pain. 87.6%, another retrospective study of focal, noncyclical pain calculated a specificity of mammography of 97% for nondense breasts and 96% for dense breasts [9]. Additionally, Tumyan et al [38] in a retrospective study of mammography in combination with US found a NPV of 100%, though the study was limited by a significant number of patients being lost to follow-up. A mammogram should be obtained if the patient has not undergone mammography within the last 3 to 6 months.


Breast Pain

Breast Pain. DBT DBT While there is no literature specifically evaluating the use of DBT in the workup of focal and noncyclical breast pain, DBT can be useful in the diagnostic setting and is known to improve lesion characterization in noncalcified lesions when compared to conventional mammographic workup [28-30].


Breast Pain

Breast Pain. US Breast While there are few studies evaluating US independently of mammography in the setting of focal and noncyclical breast pain, the existing literature suggests that US may be useful to exclude malignancy in these cases. A retrospective review of 110 cases of focal breast pain evaluated by US found no imaging abnormality in 85 cases (77.3%) [12], and there were no malignancies. In 15 cases (13.6%), cysts were identified, and of those, 3 patients (2.7%) had solid masses, all of which were benign. Fluid collections and edema were seen in the remaining cases.


Breast Pain

Breast Pain. Several studies have evaluated the usefulness of US in addition to mammography in cases of focal, noncyclical breast pain and concluded that in the setting of a negative mammogram, US may not be indicated, especially in patients with nondense breasts. A retrospective study of 206 patients with focal breast pain as their only symptom evaluated with US after a mammogram, found that US resulted in 8 additional biopsies and 14 additional 6-month follow-up examinations without detecting any additional cancers [11]. Another retrospective study found 76 imaging abnormalities in 413 cases of focal pain, with 46 (61%) seen on US alone, for a specificity of 82%. While there were no malignancies, US found a benign lesion in 40 of 56 cases in which mammography was negative in patients with dense breasts and found a benign lesion in 6 of 20 cases with a negative mammogram and nondense breasts. The specificity of US was 95% for nondense breasts and 87% for dense breasts [9].


Breast Pain

Breast Pain. Some authors suggest that, despite the low incidence of malignancy, US may be useful in that it could potentially find treatable causes of breast pain, such as cysts [9]. On the other hand, a prospective, observational follow-up study of 987 patients with breast pain alone found benign findings in 8.6% of cases, which consisted mostly of small cysts [14]. The authors argued that in the absence of a palpable abnormality, any cyst that may be found by US would unlikely be large enough to cause pain or benefit from aspiration.


Breast Pain

Breast Pain. If a mammogram has been obtained within the last 3 to 6 months, the patient may proceed directly to US.


Breast Pain

Breast Pain. MRI Breast There is no relevant literature regarding the use of MRI in the evaluation of focal and noncyclical breast pain.


Breast Pain

Breast Pain. Sestamibi MBI There is no relevant literature regarding the use of MBI in the evaluation of focal and noncyclical breast pain.


Breast Pain

Breast Pain. Although there are references that report on studies with design limitations, 6 good-quality studies provide good evidence.


Breast Pain

Breast Pain. Breast Pain Supporting Documents For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Introduction/Background Liver function tests are often obtained as part of standard laboratory panels in asymptomatic and symptomatic patients. Alteration in the biochemical markers of hepatocyte damage or bile flow indicate hepatobiliary insult rather than a measurement of liver function. Routine liver chemistries include alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. On the contrary, albumin and prothrombin time are actual markers of hepatocellular synthetic function.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. The severity of abnormal aminotransferase can be classified as 1) mild: <5 times the upper reference limit, 2) moderate: 5 to 10 times the upper reference limit, or 3) severe: >10 times the upper reference limit. Moderate and severe are discussed collectively as significant clinical overlap exists between these 2 categories.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Pathologically increased levels of ALP may occur in cholestatic liver disease, which can show elevated ALP with or without elevated bilirubin. Cholestasis can be due to obstruction of biliary outflow or impairment in bilirubin uptake. If abnormal ALP levels are seen without impairment of other liver enzymes, the etiology is suspected to be cholestatic in origin. If ALP is elevated in isolation, a confirmation with gamma-glutamyl transpeptidase (GGT) or fractionated ALP isoenzyme helps to differentiate hepatic from nonhepatic etiologies, such as bone disease. GGT can be elevated in nonhepatic diseases such as myocardial infarction, renal failure, diabetes, pulmonary, and pancreatic disorders; therefore, it is not used in isolation to assess for liver disease when other liver function tests are normal [1].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Bilirubin is produced by the breakdown of heme. Following conjugation within the liver to increase water solubility, bilirubin is excreted into bile. Conjugated (direct) bilirubin is rapidly excreted in the alimentary tract; thus, bilirubin amounts are negligible in serum in healthy individuals. A rise in levels of conjugated bilirubin in the serum is an indicator of impaired liver excretion. Conjugated hyperbilirubinemia can occur because of impaired bilirubin transport into the intrahepatic bile ducts or downstream obstruction of the biliary tract from intrinsic or extrinsic causes.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. aUniversity of Arizona, Banner University Medical Center, Tucson, Arizona. bUniversity of Alabama Medical Center, Birmingham, Alabama. cPanel Chair, Johns Hopkins University School of Medicine, Baltimore, Maryland. dDuke University Medical Center, Durham, North Carolina. eOregon Health & Science University, Portland, Oregon. fPerelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; American Association for the Study of Liver Diseases. gUniversity of Alabama at Birmingham, Birmingham, Alabama, Primary care physician. hUniversity of Connecticut, Farmington, Connecticut. iUniversity of Alabama at Birmingham Medical Center, Birmingham, Alabama. jJohns Hopkins Bayview Medical Center, Baltimore, Maryland; Commission on Nuclear Medicine and Molecular Imaging. kNorthShore University HealthSystem, Evanston, Illinois. lNew York University Langone Medical Center, New York, New York. mUniversity of Cincinnati Medical Center, Cincinnati, Ohio. nCleveland Clinic, Cleveland, Ohio; American College of Physicians, Hospital Medicine. oJohns Hopkins Hospital, Baltimore, Maryland. pSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Reprint requests to: publications@acr.org


Abnormal Liver Function Tests

Abnormal Liver Function Tests

Abnormal Liver Function Tests. Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Serum unconjugated (indirect) bilirubin can be increased in hemolysis or Gilbert syndrome, which is diagnosed when unconjugated hyperbilirubinemia is the only abnormal liver function test and conjugated bilirubin and complete blood count are normal.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. OR Discussion of Procedures by Variant Variant 1: Abnormal liver function tests. Hepatocellular predominance with mild aminotransferase increase. Initial imaging. Hepatocellular predominant liver chemistry is seen when aminotransferases are elevated much higher than ALP (cholestatic-pattern). Hepatocellular injury causes the release of ALT and AST in serum.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Increase in ALT (mild or moderate to severe) is directly linked to hepatocyte injury. In addition to fatty liver disease, other causes of rising ALT include acute or chronic viral hepatitis, acute Budd-Chiari syndrome, ischemic hepatitis, autoimmune, hemochromatosis, medications/toxins, autoimmune, alpha1-antitrypsin deficiency, and Wilson disease. AST levels are also increased in fatty liver disease and cirrhosis. However, if the aminotransferase rise is predominantly AST, nonhepatic causes (hemolysis, myopathy, thyroid disease, exercise) should also be considered.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Common causes of mild increases in aminotransferases are nonalcoholic fatty liver disease (NAFLD) and alcohol- induced liver disease; uncommon causes include drug-induced liver injury, hepatitis B, hepatitis C, and hereditary hemochromatosis. Rare causes are alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. The 2 most common causes of fatty liver disease are NAFLD and alcohol-induced steatosis/steatohepatitis. Excessive intake of alcohol results in alcohol-induced fatty liver disease. The AST:ALT ratio is generally >2 in alcohol-induced fatty liver disease and <1 in metabolic disease-related fatty liver. Alcohol-induced liver disease is caused by excess alcohol consumption, whereas the nonalcoholic variant is related to insulin resistance and the metabolic syndrome. NAFLD is the most common liver disease in first world countries, with a prevalence of 20% to 30% in the general population; however, this increases to 70% with obesity and 90% with diabetes mellitus.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. NAFLD is a spectrum of fat deposition and hepatic inflammation followed by fibrosis due to metabolic insults. Simple hepatic steatosis can be seen in 70% to 75% of cases without cellular insult. Nonalcoholic steatohepatitis (NASH) can be found in 25% to 30% of cases with hepatocyte injury and inflammation due to lipid; these entities, simple hepatic steatosis and NASH, can coexist. Progressive insults with inflammation can result in fibrosis leading to cirrhosis and hepatocellular carcinoma [4,5].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Abdomen Ultrasound (US) is useful as a first-line investigation tool for mild increase in liver enzymes. US has been used world-wide to screen for both alcohol-induced liver disease and NAFLD. US has the benefit of being noninvasive and is an accurate method to detect steatosis [6,7].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US can be successfully diagnose hepatic lipid content of >33% but can be unreliable with mild fatty infiltration, with an 84.8% sensitivity and a 93.6% specificity with US in moderate and sever hepatic fat deposition (defined as >30% by histology) [8,9].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Both sensitivity and specificity declined to 53.3% to 65% and 77% to 81.2%, respectively, when mild steatosis was included with moderate and severe degrees of steatosis. It is noteworthy that sonographic specificity further deteriorates with confounding factors such as inflammation or fibrosis within the liver parenchyma [8,10,11].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Estimation of hepatic steatosis on conventional US is subjective and challenged by inter- and intraobserver variability. Normal liver shows echogenicity similar to or just higher than normal renal cortex. Fatty infiltration


Abnormal Liver Function Tests

Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. increases the echogenicity of the liver parenchyma. Hepatic steatosis can be graded as mild, moderate, and severe: 1) mild: mild diffuse increase in liver echogenicity and clear definition of the diaphragm and intrahepatic vessel walls; 2) moderate: mild diffuse increase in liver echogenicity and obscuration of the diaphragm and intrahepatic vessel walls; and 3) severe: marked increase in liver echogenicity leading to nonvisualization of diaphragm and intrahepatic vessel walls [12].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Instead of qualitative assessment of liver and kidney parenchyma, quantitative grading can be done to obtain hepatorenal index. Mancini et al and Webb et al have shown an excellent correlation of mild steatosis quantified on hepatorenal index to fat fraction on MR spectroscopy and liver biopsy, with the area under the curve measuring up to 99.2% and 99.6%, respectively. The hepatorenal index is independent of confounding factors including high body mass index, inflammation, or fibrosis [13,14].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Abdomen with IV Contrast Cocciolillo et al [15] showed hepatic blood flow derangements in the portal vein and liver parenchyma using contrast-enhanced US (CEUS). The percentage of maximal contrast activity, regional blood volume (cubic centimeters) and regional blood flow (cubic centimeters per second) was reduced in NASH and NAFLD compared with controls. CEUS can be added to conventional US and US shear wave elastography; however, there is no evidence in the current literature to support the use of CEUS in this clinical scenario.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Duplex Doppler Abdomen Duplex Doppler may be added as adjunct to conventional US B-mode images. The normal triphasic flow pattern in right hepatic vein flow may become monophasic following intrahepatic fat deposition or, occasionally, by inflammatory or fibrotic changes [16]. Tarzamni et al [17] found an increase in the arterial resistive index and no change in pulsatility index and portal venous velocity in patients with NAFLD with favorable response to treatment.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Shear Wave Elastography Abdomen US shear wave elastography is increasingly used to assess liver stiffness in chronic liver parenchymal disease. Various US elastography techniques have evolved in recent years that use different shear wave generation and propagation. These include transient elastography, acoustic radiation force impulse elastography, supersonic shear wave, and real-time tissue elastography.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Controlled attenuation parameter is a novel method for the measurement of hepatic steatosis that uses the same radiofrequency data used for quantification of liver stiffness. Shi at al [18] performed a meta-analysis to look at performance of controlled attenuation parameter in detection of severity of steatosis (>S1, >S2, >S3). The sensitivity and specificity were 78% and 79% for S1, 85% and 79% for S2 and, 83% and 79% for S3 steatosis, respectively. Receiver operating characteristic analysis was 85% for >S1, 88% for >S2, and 87% for >S3. According to the meta- analysis, controlled attenuation parameter has a good sensitivity and specificity for detecting hepatic fat content; however, accuracy is limited.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. However, CT is not useful as the first modality of choice for the diagnosis of mildly elevated aminotransferases due to mild fatty infiltration for multiple reasons, including failure to detect early steatosis, lack of accuracy, and reliability [20,23,24].


Abnormal Liver Function Tests

Abnormal Liver Function Tests

Abnormal Liver Function Tests. Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in this clinical scenario.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MR Elastography Abdomen MR elastography is the most useful modality to estimate liver fibrosis. MR elastography is currently being investigated to diagnose NAFLD without liver fibrosis and therefore is not an initial investigation. Chen et al [27] showed higher liver stiffness in patients with steatosis and lobular inflammation than in those with steatosis and lower stiffness when compared with those with parenchymal fibrosis in fatty liver.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Chemical shift imaging using T1 gradient echo exploits the differences in the resonance frequencies of water and fat proton signals yielding 2-point Dixon T1 in-phase and opposed-phase with fat and iron depiction. However, T2* decay from hepatic iron can erroneously lead to an underestimation of liver fat content by reducing in-phase signal, particularly at longer time to echo [28-31].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Proton density fat fraction is a quantitative and reproducible method for fat estimation that uses chemical shift while eliminating or reducing the effects of confounding factors, such as T2 decay. Proton density fat fraction is an accurate (area under the receiver operating characteristic curve = 98.9%; 95% confidence interval, 96.8%-100%) and reliable tool for hepatic lipid assessment (grade 1 or higher) across different vendors and magnetic field strengths. Recent investigations suggest that quantitative MR methods may serve as a comparable or even better reference standard for fat quantification to reference standard liver biopsy [32,33].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MRI Abdomen Without and With IV Contrast With MRCP There is no relevant literature to support the use of MRI abdomen without and with IV contrast with MR cholangiopancreatography (MRCP) in this clinical scenario.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Variant 2: Abnormal liver function tests. Hepatocellular predominance with moderate or severe aminotransferase increase. Initial imaging. Breu et al [34], in a large multicenter study, found ischemic hepatitis to be the most common cause for markedly elevated aminotransferase ALT/AST level (5000 IU/L). Ischemic liver injury is a serious condition because it can progress to liver failure and high mortality [35]. Acute viral hepatitis (hepatitis A and B, hepatitis C), drug-induced liver injury (acetaminophen), and pancreaticobiliary pathologies leading to biliary obstruction and liver injury are other causes of moderate to marked increase in aminotransferases [34].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis Without IV Contrast Although intra- and extrahepatic biliary ductal dilatation may be identified on CT abdomen and pelvis without IV contrast, contrast confers added benefit for assessment of ischemic liver injury and possible useful hemodynamic information, such as sequela of portal hypertension or hepatic congestion.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. There are advantages to including the pelvis in the CT abdomen and pelvis examination, including detecting pelvic ascites, pelvic collateral vessels in portal hypertension, and possible sources of obstruction (eg, lymphadenopathy).


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis With IV Contrast Although the findings of acute hepatitis on CT are not specific for the diagnosis, CT may be useful for evaluating the sequela or complications of hepatitis. CT with IV contrast can also identify ischemic hepatitis.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Acute hepatitis on contrast-enhanced CT demonstrates arterial heterogeneity, periportal hypoattenuation, perihepatic lymphadenopathy (>7 mm), and ascites in decreasing order of prevalence [37]. A thickened gallbladder


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Abnormal Liver Function Tests wall on contrast-enhanced CT (mean 5.2 mm) was an independent predictor of severe hepatitis and prolonged cholestasis [37].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. An association of enhanced CT findings with phases of acute hepatitis (prodrome, jaundice, recovery) showed small hepatoduodenal lymphadenopathy, perihepatic fat infiltration, gallbladder wall thickening, contraction, or an undulating inner margin, periportal edema, hepatomegaly, splenomegaly, and pelvic fluid collection in 98.8%, 76.5%, 75.3%, 43.5%, 22.4%, 52.9%, and 56.5% of the patients, respectively [38,39].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Shock liver, leading to ischemic hepatitis, may be secondary to systemic hypoxic or hypotensive causes leading to hypoperfusion of the liver, which may show hypoenhancement of a portion of the liver or entire liver parenchyma. Selective hepatic hypoperfusion due to hepatic arterial of portal venous occlusion could be reversible because of dual blood supply but may result in liver failure or hepatic infarction [40].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. There are advantages to including the pelvis in the CT abdomen and pelvis examination, including detecting pelvic ascites as well as collateral vessels in instances of portal venous hypertension.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis Without and With IV Contrast CT of the abdomen and pelvis with and without IV contrast is not typically useful for this clinical scenario because there is no benefit from adding unenhanced images.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MR Elastography Abdomen Currently there is no role for MR elastography to diagnose acute hepatic inflammation from various causes. Superimposed acute inflammation in chronic viral hepatitis does not impact correlation of stiffness with stage of fibrosis [41,42].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MRI Abdomen with MRCP Although abdominal US is the preferred modality of choice in severely elevated aminotransferase, MRI with IV contrast can be obtained to assess parenchymal inflammation, perfusion, and vascular patency.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Inflamed liver parenchyma shows increased signal intensity on T2-weighted images and decreased signal on T1- weighted images with heterogeneous perfusion, similar to CT. Periportal edema can be appreciated as a hyperintense signal on T2-weighted images. Heterogeneous enhancement of the liver in the arterial phase is seen in acute hepatic inflammation from various causes [43-48].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Perihepatic fluid and gallbladder wall edema can be seen on T2-weighted images in acute hepatitis. Hepatic capsular edema may be present in fulminant hepatitis with resultant heterogeneous enhancement on postgadolinium T1- weighted images. Hepatic infarction is seen as nonenhancing wedge-shaped hepatic parenchyma. Vascular cause for ischemic hepatitis can be identified on postcontrast imaging, including MR angiogram [38,49].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Several investigations have shown impaired uptake of liver-specific agents in hepatic dysfunction. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid is a paramagnetic hepatobiliary MR contrast agent, which (due to its OATP1B1/B3-dependent hepatocyte-specific uptake and paramagnetic properties) is used for evaluation of liver function analysis [50-53].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Abdomen with IV Contrast CEUS is not a first-line imaging modality to assess the hepatic parenchyma in acute severe hepatitis or ischemia. Investigations to use as adjunct to check vascular patency in transplant livers has been tried [60], but there is a lack of relevant literature to support the use of CEUS in this clinical scenario.


Abnormal Liver Function Tests

Abnormal Liver Function Tests

Abnormal Liver Function Tests. Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Duplex Doppler Abdomen Duplex Doppler can be added to routine grayscale US to look for vascular patency in patients with suspected ischemic insult.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Shear Wave Elastography Abdomen There is no relevant literature to support the use of US shear wave elastography in toxic or ischemic liver injury.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Choledocholithiasis is the most common cause of extrahepatic biliary obstruction and elevated ALP of liver origin. Additional etiologies of extrahepatic biliary obstruction include malignant obstruction, biliary strictures, and infections (eg, AIDS cholangiopathy, and liver flukes). Isolated elevated ALP of hepatic origin (without other elevated liver function tests) that persists over time suggests a chronic cholestatic process, such as partial bile duct obstruction, primary biliary cholangitis, primary sclerosing cholangitis, or drug-induced cholestasis. Infiltrative liver diseases such as sarcoidosis, amyloidosis, and hepatic metastases, among others, may also lead to intrahepatic cholestasis. ALP may also be elevated nonspecifically in addition to other elevated liver biochemical tests in all types of liver diseases, including hepatitis, cirrhosis, sepsis, and heart failure.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis With IV Contrast Although abdominal US is typically the first-line imaging modality for identifying biliary obstruction, contrast- enhanced CT of the abdomen and pelvis may help define the site of obstruction, potential etiology, and coexistent complications [63]. CT is considered less sensitive than MRI with MRCP for the evaluation of the bile ducts; however, CT may provide useful information regarding the etiology of cholestasis.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. There are advantages to including the pelvis in the CT abdomen and pelvis examination, including detecting pelvic ascites, pelvic collateral vessels in portal hypertension, and possible sources of obstruction (eg, lymphadenopathy).


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis Without and With IV Contrast CT of the abdomen and pelvis with and without IV contrast is not typically performed for this clinical scenario because there is no benefit from adding unenhanced images.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis Without IV Contrast Although intra- and extrahepatic biliary ductal dilatation may be identified on CT abdomen and pelvis without IV contrast, contrast confers added benefit for assessment of ischemic liver injury and possible useful hemodynamic information, such as sequela of portal hypertension or hepatic congestion.


Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MR Elastography Abdomen MR elastography is currently the most accurate imaging modality for the diagnosis and staging of hepatic fibrosis; however, it has a limited to no role in the initial imaging of suspected cholestasis.


Abnormal Liver Function Tests

Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MRI Abdomen Without and With IV Contrast With MRCP Abdominal US is typically the first-line imaging modality; however, in the setting of persistently elevated ALP and a negative abdominal sonogram, MRI abdomen without and with IV contrast with MRCP may be useful. Sustained elevation of ALP is significantly correlated with choledocholithiasis on MRCP and may be helpful for triaging patients to endoscopic retrograde cholangiopancreatography (ERCP); however, patients who have common bile duct stones demonstrated on US should proceed directly to ERCP [64,65].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. If extra- or intrahepatic biliary ductal dilatation is identified on abdominal US, contrast-enhanced MRI with MRCP is the most useful imaging modality for evaluating the etiology of biliary obstruction. Contrast-enhanced MRI with MRCP facilitates noninvasive evaluation of both intra- and extrahepatic bile ducts, as well as the liver parenchyma [66]. Further, contrast-enhanced MRI with MRCP enables triaging of patients to subsequent interventions, such as stenting with ERCP, brushings by endoscopic US, and image-guided or laparoscopic biopsy, as well as serving as a guide for the subsequent approach with these interventions. MRI performed with diffusion sequences and hepatobiliary contrast agents can be advantageous in lesion detection and characterization, although a decreased uptake of hepatobiliary agents by hepatocytes might decrease diagnostic accuracy, especially in patients with reduced liver function [51].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MRI Abdomen Without IV Contrast With MRCP Although less sensitive than contrast-enhanced MRI, a noncontrast MRI (including MRCP) may be useful for identifying biliary obstruction as a source of cholestasis. Contrast administration improves the sensitivity for detection of acute cholangitis, hepatic metastases, and the detection of primary sclerosing cholangitis. Furthermore, excretion of hepatobiliary contrast and opacification of the biliary ducts and gallbladder provide additional information regarding the site and etiology of obstruction, as well as liver function [67-69].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Abdomen Patients with elevated ALP suspected to be liver in origin and no alternative etiology should undergo transabdominal US to assess for dilated intra- or extrahepatic ducts and gallstones as the possible cause. Gallstone disease is prevalent with approximately 10% of adults having cholelithiasis and approximately 500,000 cholecystectomy operations performed annually [70]. Approximately 18% of adults undergoing cholecystectomy have choledocholithiasis [71,72]. Although abdominal US has a low sensitivity for detection of choledocholithiasis, in part related to frequent overlying bowel gas, it has high specificity [65]. When biliary obstruction is identified on abdominal US, frequently dynamic contrast-enhanced CT, MRI, or CEUS is required for further evaluation of the cause and possibly procedure planning. The absence of gallstones or choledocholithiasis suggests a nongallstone etiology and a normal caliber of the extrahepatic bile duct suggests intrahepatic cholestasis [71-73].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Abdomen with IV Contrast For initial imaging, there is currently no role for CEUS in the evaluation of cholestasis. CEUS has been assessed for the evaluation of liver fibrosis, which may nonspecifically elevate ALP, and is used in the characterization of potentially obstructing hepatic lesions. Similar to CT and MRI perfusion techniques, CEUS uses contrast media transit characteristics to make deductions about liver hemodynamics that relate to the presence and severity of liver fibrosis and for the characterization of hepatic lesions.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Duplex Doppler Abdomen There is debate regarding the diagnostic value of adding Doppler US to the US abdomen examination for initial imaging. Doppler US can demonstrate hemodynamic alterations related to infection (such as elevated velocity in the main hepatic artery in acute cholecystitis) or indicative of portal hypertension as seen in fibrosis or infiltrative liver diseases. The diagnostic value of Doppler US of the portal vein for the evaluation of liver function is still controversial [74].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Shear Wave Elastography Abdomen There is no relevant literature to support the use of US shear wave elastography in the evaluation of cholestasis. US shear wave elastography is used to assess for evaluation of liver fibrosis, which may nonspecifically elevate ALP; however, it has a limited to no role in the initial imaging of suspected cholestasis.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Abdomen US is the most useful imaging modality to evaluate conjugated hyperbilirubinemia due to liver parenchymal cause (alcoholic or viral hepatitis and cirrhosis) or biliary obstruction. US shows a positive predictive value of 98% and a sensitivity in the range of 65% to 95% for the diagnosis of liver parenchymal disease. Biliary obstruction can be demonstrated on US with a wide range of sensitivity (32%-100%) and specificity (71%-97%); however, the cause for distal obstruction may be obscured by overlying bowel gas [54].


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Abdomen with IV Contrast There is no relevant literature to support the use of CEUS in this clinical scenario.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. caxuda US Duplex Doppler Abdomen US duplex Doppler abdomen is not useful for this clinical scenario.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. US Shear Wave Elastography Abdomen US shear wave elastography is not useful as the first-line imaging modality to assess hyperbilirubinemia. Liver fibrosis can be demonstrated using elastography techniques with improved accuracy in higher stages of fibrosis (area under the curve, 0.88 and 0.91 for S2 and S4 fibrosis, respectively) [18]. There is no evidence to support use of US shear wave elastography in biliary obstruction.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis With IV Contrast CT abdomen with IV contrast can be used to look for morphologic changes of chronic liver parenchymal disease and its complications. CT can help identify the site of obstruction and the potential etiologies. MRI with MRCP is superior to evaluate the biliary system. Malignant biliary strictures can be identified with a high sensitivity (95%), specificity (93.35%), and accuracy (88.5%) on CT [79].


Abnormal Liver Function Tests

Abnormal Liver Function Tests

Abnormal Liver Function Tests. Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT abdomen with IV contrast is very accurate for diagnosis and staging of pancreaticobiliary malignancies, which can present with hyperbilirubinemia. Tumor resectability and surgical planning for both pancreatic and biliary cancers can be done using CT. There are advantages to including the pelvis in the CT abdomen and pelvis examination, including detecting lymphadenopathy and pelvic ascites.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis Without and With IV Contrast CT of the abdomen and pelvis with and without IV contrast is not typically useful for this clinical scenario because there is no benefit from adding unenhanced images.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. CT Abdomen and Pelvis Without IV Contrast Unenhanced CT has limited utility in assessing biliary obstruction (including etiologies) and liver fibrosis.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. MRI Abdomen with MRCP As discussed in Variant 3 above, MRI with MRCP is the most useful for evaluating the etiology of biliary obstruction. Contrast is helpful to look for cholangitis and assess malignant etiologies of biliary obstruction.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Abnormal Liver Function Tests

Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. 12 2. Neuschwander-Tetri BA, Unalp A, Creer MH, Nonalcoholic Steatohepatitis Clinical Research N. Influence of local reference populations on upper limits of normal for serum alanine aminotransferase levels. Arch Intern Med 2008;168:663-6. 3. Pettersson J, Hindorf U, Persson P, et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol 2008;65:253-9. 4. Arshad T, Golabi P, Henry L, Younossi ZM. Epidemiology of Non-alcoholic Fatty Liver Disease in North America. Curr Pharm Des 2020;26:993-97. 5. Cotter TG, Rinella M. Nonalcoholic Fatty Liver Disease 2020: The State of the Disease. Gastroenterology 2020;158:1851-64. 6. Chen CL, Cheng YF, Yu CY, et al. Living donor liver transplantation: the Asian perspective. Transplantation 2014;97 Suppl 8:S3. 7. Singh D, Das CJ, Baruah MP. Imaging of non alcoholic fatty liver disease: A road less travelled. Indian J Endocrinol Metab 2013;17:990-5. 8. Hernaez R, Lazo M, Bonekamp S, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011;54:1082-90. 9. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002;123:745-50. 10. Lee SS, Park SH, Kim HJ, et al. Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol 2010;52:579-85. 11. van Werven JR, Marsman HA, Nederveen AJ, et al. Assessment of hepatic steatosis in patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo MR imaging, and point-resolved 1H MR spectroscopy. Radiology 2010;256:159-68. 12. Walas MK, Skoczylas K, Gierblinski I. Standards of the Polish Ultrasound Society - update. The liver, gallbladder and bile ducts examinations. J Ultrason 2012;12:428-45. 13. Mancini M, Prinster A, Annuzzi G, et al. Sonographic hepatic-renal ratio as indicator of hepatic steatosis: comparison with (1)H magnetic resonance spectroscopy. Metabolism 2009;58:1724-30. 14. Webb M, Yeshua H, Zelber-Sagi S, et al. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol 2009;192:909-14. 15. Cocciolillo S, Parruti G, Marzio L. CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. World J Hepatol 2014;6:496-503. 16. Dietrich CF, Lee JH, Gottschalk R, et al. Hepatic and portal vein flow pattern in correlation with intrahepatic fat deposition and liver histology in patients with chronic hepatitis C. AJR Am J Roentgenol 1998;171:437-43. 17. Tarzamni MK, Khoshbaten M, Sadrarhami S, et al. Hepatic Artery and Portal Vein Doppler Indexes in Non- alcoholic Fatty Liver Disease Before and After Treatment to Prevent Unnecessary Health Care Costs. Int J Prev Med 2014;5:472-7. 18. Shi KQ, Tang JZ, Zhu XL, et al. Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: a meta-analysis of diagnostic accuracy. J Gastroenterol Hepatol 2014;29:1149-58. 19. Lawrence DA, Oliva IB, Israel GM. Detection of hepatic steatosis on contrast-enhanced CT images: diagnostic accuracy of identification of areas of presumed focal fatty sparing. AJR Am J Roentgenol 2012;199:44-7. 20. Park SH, Kim PN, Kim KW, et al. Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology 2006;239:105-12. 21. Kodama Y, Ng CS, Wu TT, et al. Comparison of CT methods for determining the fat content of the liver. AJR Am J Roentgenol 2007;188:1307-12. 22. Ricci C, Longo R, Gioulis E, et al. Noninvasive in vivo quantitative assessment of fat content in human liver. J Hepatol 1997;27:108-13. 23. Birnbaum BA, Hindman N, Lee J, Babb JS. Multi-detector row CT attenuation measurements: assessment of intra- and interscanner variability with an anthropomorphic body CT phantom. Radiology 2007;242:109-19. 24. Koplay M, Sivri M, Erdogan H, Nayman A. Importance of imaging and recent developments in diagnosis of nonalcoholic fatty liver disease. World J Hepatol 2015;7:769-76. 25. Johnston RJ, Stamm ER, Lewin JM, Hendrick RE, Archer PG. Diagnosis of fatty infiltration of the liver on contrast enhanced CT: limitations of liver-minus-spleen attenuation difference measurements. Abdom Imaging 1998;23:409-15. 26. Li Q, Dhyani M, Grajo JR, Sirlin C, Samir AE. Current status of imaging in nonalcoholic fatty liver disease.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Abnormal Liver Function Tests World J Hepatol 2018;10:530-42.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Introduction/Background Total knee arthroplasty (TKA), primarily used to treat pain and improve function in patients with symptomatic advanced knee osteoarthritis, is the most commonly performed joint replacement procedure in the United States [1,2]. In 2012, >670,000 knee replacement procedures were performed in the United States [3], which represents an increase of 86% since 2003 [4]. It is estimated that 4 million patients in the United States are currently living with a knee replacement [5]. By 2030, it is estimated that the annual demand for primary TKA will grow by 673% to 3.48 million [6]. Factors contributing to the rising number of TKAs include population growth; aging and increased longevity of the population; expanded indications for performing TKA, especially in individuals >65 years of age; obesity; decline in postprocedure complications; and increased patient demand [7].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Special Imaging Considerations In some patients with knee arthroplasties, repeated hemarthroses are caused by synovial hyperemia or true arteriovenous malformations. These patients can be successfully diagnosed with angiography and treated with embolization. In rare instances, geniculate and popliteal vessel injuries may occur during surgery [15].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. A recent study reports single-photon emission CT (SPECT)/CT arthrography with Tc-99m sulfur colloid has a high diagnostic accuracy (97%) in the evaluation of loosening of both hip and knee arthroplasties in patients with persistent postprocedural pain [16]. Barnsley et al [17] also found arthrography with SPECT/CT to be an accurate means of identifying aseptic prosthetic joint loosening.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. aPenn State Milton S. Hershey Medical Center, Hershey, Pennsylvania and Uniformed Services University of the Health Sciences, Bethesda, Maryland. bPanel Chair, Mayo Clinic Arizona, Phoenix, Arizona. cUniversity of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. dPenn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania. eMayo Clinic, Rochester, Minnesota. fEmory University, Atlanta, Georgia; Committee on Emergency Radiology-GSER. gHospital for Special Surgery, New York, New York. hPenn State Health, Hershey, Pennsylvania, Primary care physician. iDuke University Medical Center, Durham, North Carolina. jUniversity of Missouri Health Care, Columbia, Missouri. kSpecialty Chair, University of Kentucky, Lexington, Kentucky.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Reprint requests to: publications@acr.org


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. OR Discussion of Procedures by Variant Variant 1: Follow-up of symptomatic or asymptomatic patients with a total knee arthroplasty. Initial imaging. 3-Phase Bone Scan Knee There is insufficient evidence to support the use of 3-phase bone scan for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Arthrography Knee There is insufficient evidence to support the use of CT arthrography for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Knee With IV Contrast There is insufficient evidence to support the use of CT with intravenous (IV) contrast for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Knee Without and With IV Contrast There is insufficient evidence to support the use of CT without and with IV contrast for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Knee Without IV Contrast There is insufficient evidence to support the use of CT without IV contrast for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. FDG-PET/CT Whole Body There is insufficient evidence to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Fluoride PET/CT Whole Body There is insufficient evidence to support the use of fluoride PET/CT for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Fluoroscopy Knee There is insufficient evidence to support the use of fluoroscopy for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Image-Guided Aspiration Knee There is insufficient evidence to support the use of image-guided aspiration for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. MRI Knee Without and With IV Contrast There is insufficient evidence to support the use of MRI without and with IV contrast for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. MRI Knee Without IV Contrast There is insufficient evidence to support the use of MRI without IV contrast for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Radiography Knee Radiographs can demonstrate abnormal bone and hardware alignment, periprosthetic lucencies and osteolysis [18- 24], reactive bone formation and periostitis, periprosthetic fractures, evidence of polyethylene liner wear, and cement and heterotopic bone about the knee. Radiographs can often delineate effusion, soft-tissue swelling, foreign bodies, soft tissue emphysema, heterotopic bone, and cement or metal in the soft tissues. Radiographs are useful as the initial evaluation for symptomatology or follow-up. Radiographs are often limited in terms of sensitivity, and further imaging may be required.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Routine immediate postoperative radiographs are considered unnecessary unless the surgery is complicated or there are specific clinical indications warranting imaging evaluation [25,26], because several studies have indicated that the rate of complications identified in the immediate postoperative setting is low. Ververeli et al [27] compared recovery room radiographs with additional predischarge radiographs and found no change in the postoperative management of 124 consecutive patients with TKAs and suggested eliminating the predischarge radiographs. Novack et al [25] retrospectively reviewed 4,830 consecutive patients following cemented or uncemented TKAs and concluded routine recovery room radiographs after an uncomplicated primary TKA are not a reliable mechanism for preventing mechanical complications and did not alter patient care.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Radiographic evaluation of wear is based on weightbearing AP and lateral radiographs and on axial radiographs. Liner wear is seen as joint space narrowing, varus or valgus deformity, or patellar tilt. An effusion may be present. Findings can be subtle and annual weightbearing radiographs are suggested for detecting subclinical wear [21]. Collier et al [36] found that 87% of measurements performed on standing frontal knee radiographs (on the basis of the minimum distance from the metallic femoral condyle to a line through the top surface of the baseplate at its widest dimension) were within 1 mm of the known implant thickness, but the accuracy decreased for evaluating polyethylene thickness in patients with wear requiring revision.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Instability is evaluated on radiographs obtained in extension-flexion position, under varus-valgus stress, and during anterior and posterior drawer maneuvers. In contrast, malalignment refers to suboptimal alignment of the prosthesis components relative to each other (although it is occasionally used to describe alignment of the bones in relation to each other and to the joint) [37] and is evaluated on full-length standing radiographs of the lower extremity [21].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Radiographs including the entire prosthesis are the initial examination for assessment of suspected periprosthetic fractures. Radiographs are also usually satisfactory for assessment of patellar complications [20] and helpful in guiding treatment [38]. Axial radiographs demonstrate the degree of patellar tilt or subluxation [21]. Baldini et al [39] proposed a weightbearing axial radiograph to better assess patellofemoral kinematics.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Although axial radiographs may be used to determine axial rotation of the femoral component [40], CT is most commonly used for this purpose. Leon-Munoz et al [41] have noted CT-scan-based 3-D models and, therefore, supine CT scan, underestimate the degree of deformity at the knee joint, both in varus and valgus; therefore


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty preoperative full-leg standing radiographs should be performed for patient-specific instrumentation assisted TKAs, as a complementary study, to analyze the position of the load-bearing axis.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Radiographs cannot directly image post-TKA periprosthetic soft-tissue abnormalities. However, radiographic signs of extensor mechanism tendon tears include patella alta, patella baja, localized soft-tissue swelling, posterior subluxation of the tibia, bony avulsions, and dystrophic calcifications within the tendon [21,42].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. US Knee There is insufficient evidence to support the use of ultrasound for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. WBC Scan and Sulfur Colloid Scan Knee There is insufficient evidence to support the use of white blood cell (WBC) scan and sulfur colloid scan for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Variant 2: Suspected infection after total knee arthroplasty. Additional imaging following radiographs. Infection is a serious complication of joint arthroplasty and is reported in 0.8% to 1.9% of TKAs [43]. The frequency of infection is increasing as the number of primary arthroplasties increases [44]. Infection may be acute or delayed, with delayed infection defined as occurring at least 3 months postoperatively [45]. In a series, infection was responsible for 37.6% of early revisions and 21.9% of revisions performed >2 years after the initial operation [12]. Staphylococcus aureus and coagulase-negative Staphylococcus species, including Staphylococcus epidermidis, are the most common organisms associated with these infections [46]. Both clinical findings and laboratory tests may serve useful in addition to imaging studies. Low-grade or chronic TKA infections may be difficult to diagnose preoperatively. Duff et al [18] noted that diagnosis of infection was not obvious in 53% of knees before revision arthroplasty. Pain is the most common presenting symptom of infection, but pain is a nonspecific finding [47]. In acute infection, findings such as pain, swelling, warmth, erythema, and fever are common, whereas chronic infections may be manifested by pain alone [44]. Night pain or pain at rest is characteristic of infection, whereas pain on weightbearing is more characteristic of mechanical loosening. Some authors suggest that infection needs to be excluded in all patients with pain persisting >6 months after joint replacement [18].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Arthrography Knee CT joint arthrography can assess for lucency with contrast accumulation at the bone/cement/hardware interface. These areas of lucency are not specific for infection versus mechanical loosening.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Knee With IV Contrast CT has a limited role in the workup of periprosthetic infection. CT with IV contrast could help demonstrate periprosthetic fluid collections and fistulae. Advances in metal artifact reduction may expand the potential role of CT.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Knee Without and With IV Contrast CT has a limited role in the workup of periprosthetic infection. Noncontrast CT can demonstrate the size and extent of osteolysis, periprosthetic lucencies, intraosseous or soft-tissue gas, and reactive bone formation that might not be evident on radiographs [20,67]. CT with IV contrast could help demonstrate periprosthetic fluid collections and fistulae. Advances in metal artifact reduction may expand the potential role of CT.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Knee Without IV Contrast CT has a limited role in the workup of periprosthetic infection. Noncontrast CT can demonstrate the size and extent of osteolysis, periprosthetic lucencies, intraosseous or soft-tissue gas, and reactive bone formation that might not be evident on radiographs [20,67]. Advances in metal artifact reduction may expand the potential role of CT.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. FDG-PET/CT Whole Body FDG-PET/CT scans may be useful for detecting infection after joint replacement. FDG-PET images reflect relative levels of glucose uptake and thus reflect the localized level of increased metabolic activity. Zhuang et al [68] reported that elevated glycolytic activity causes inflammatory cells such as neutrophils and activated macrophages to be FDG avid at sites of inflammation and infection. Some periprosthetic uptake may occur because of marrow activity, and adding marrow scanning can increase specificity [69]. In these instances, the marrow study would be performed the next day using a different camera type because the marrow scan relies on lower energy photons (PET, 511keV; Tc-99m, 140 keV). Zhuang et al [68] studied 36 painful knee prostheses using FDG-PET and identified 10 of 11 infected cases but had false-positive results in 7 cases (sensitivity of 90.9%, specificity of 72%, and accuracy of 77.8% for detecting infection). This was a lower accuracy than found in assessment of hip prostheses. The cause for the large number of false-positives was not known. Aksoy et al [70] found a positive predictive value (PPV) of 28% (15 of 54) for infection in 54 patients with painful joint prosthesis (24 knee, 48 hip) using FDG-PET. Manthey et al [71] reported that, by analyzing intensity and periprosthetic uptake patterns on FDG-PET, accurate differentiation among aseptic loosening, synovitis, and infection is possible. Kwee and Kwee [72] reports FDG


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty uptake at the bone-prosthesis interface has been consistently reported as diagnostic criterion for knee prosthetic joint infection. Kwee et al [73] in a meta-analysis reported that the specificity of FDG-PET for diagnosing infection was significantly lower for knee prostheses (74.8%) than for hip prostheses (89.8%). Delank et al [74], in a series of both hip and knee prostheses, found that a negative PET scan excluded infection (100% sensitivity). If the scan was positive, differentiation between wear and infection was not possible. Prandini et al [75] performed a meta- analysis of the diagnostic performance of different radiotracers in peripheral osteomyelitis and prosthetic joint infections, yielding results for FDG-PET with a sensitivity of 94%, a specificity of 87%, a PPV of 87%, an NPV of 94%, and an overall accuracy of 92%. Although metal artifacts have very little impact on nuclear medicine examinations (except as photopenic defects) and create negligible scatter [68,76,77], high PET attenuation coefficients in the area of metal can lead to an overestimation of the PET activity in that region and thereby to a false-positive PET finding. Nonattenuated PET images, which do not manifest this error, can be used in these cases to aid the interpretation of these metal-induced artifacts.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Synovitis and aseptic loosening (in hip prostheses) may cause increased FDG uptake [69]. Sterner et al [78] examined 14 patients with painful TKA to detect early aseptic loosening. Overall accuracy was 71% (sensitivity, 100%; specificity, 56%). In addition, Stumpe et al [79] found diffuse synovial and focal extrasynovial FDG uptake in patients with component malrotation. They concluded that this test is noncontributory in individual patients with persistent pain. Studies in patients with hip prostheses have shown that postoperative remodeling can result in artifactual periprosthetic FDG uptake for up to 6 months after implant insertion [80]. Noting the lack of specificity for detection of periprosthetic infection on conventional FDG-PET, Aksoy et al [70] explored the use of FDG- labeled leukocyte PET/CT for imaging patients with painful joint prostheses and found a sensitivity of 93%, a specificity of 97%, a PPV of 93%, and an NPV of 97%. However, this examination is not in general use. Basu et al [81] found the sensitivity, specificity, PPV, and NPV of FDG-PET in knee prostheses were 94.7%, 88.2%, 69.2%, and 98.4%, respectively, in 87 patients with knee prostheses suspected of being either infected or experiencing noninfectious loosening. Van Acker et al [82] investigated the use of FDG-PET in combination with bone scans and showed no advantage over HMPAO-labeled WBC and bone scans. Comparison of FDG-PET with In-111- labeled leukocyte/Tc-99m-labeled sulfur colloid marrow imaging showed that FDG-PET was less accurate than the leukocyte/marrow scans and could not replace that combination of tests [69].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Fluoride PET/CT Whole Body There is insufficient evidence to support the use of fluoride PET/CT for the initial evaluation of TKA.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty as a month may be necessary for cultures of aspirated fluid to become positive [30]. Weekly repeat aspirations may be needed if the first aspiration is negative and clinical suspicion for infection remains high. Even with a negative preoperative aspiration, intraoperative tissue may indicate infection. Bernard [50], after literature review and a multicenter trial, advocated CRP and joint aspiration as the best tools for diagnosing prosthetic joint infection. When the CRP level is >10 mg/L, repeat joint aspiration or biopsy is suggested. Della Valle [90] also found the combination of ESR and CRP to be a good screening tool for infection, with only one infected knee having negative results on both tests. These authors suggest preoperative aspiration if the ESR or CRP is elevated or if clinical suspicion is high, combined with intraoperative frozen section analysis of the periprosthetic synovial tissue [90]. The AAOS gives a moderate strength of recommendation for synovial fluid testing including leukocyte count and neutrophil percentage, aerobic and anaerobic bacterial cultures, leukocyte esterase, alpha-defensin, CRP, and nucleic acid amplification testing (eg, polymerase chain reaction) for bacteria [54]. A recent manuscript advises intraoperative synovial fluid re-cultures are necessary even if the preoperative aspiration culture is positive and any discordance between preoperative aspiration culture and intraoperative synovial fluid culture should be noted [91]. If the joint aspirate culture is positive on the basis of both cell count with differential and positive cultures, then infection is considered likely and treatment is initiated [54,92]. In that setting, no further imaging is supported for the diagnostic workup of the infection. Berbari [46] studied 897 cases of periprosthetic joint infection and found that approximately 7% were associated with negative cultures. If the preoperative synovial cultures remain negative, multiple intraoperative periprosthetic tissues should be submitted for aerobic and anaerobic bacterial culture [54].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. MRI Knee Without and With IV Contrast MRI may have a role in the workup of periprosthetic infection. Advances in metal artifact reduction may expand the potential role of MRI. Using metal reduction techniques, Potter and Foo found that infected synovium has hyperintense laminar appearance, distinct from the appearance of particle disease [22,93]. They noted that, in selected cases, MRI may be helpful in detecting extracapsular spread of infection and abscess formation. IV contrast may provide additional benefit in this regard [93]. On the basis of their findings, Plodkowski [94] examined 28 patients with proven infected TKAs and 28 controls with noninfected TKA. They found a sensitivity of 86% to 92% and a specificity of 85% to 87%, with almost perfect interobserver agreement, when using the appearance of lamellated hyperintense synovitis to classify infected versus noninfected TKA. Li [95] also reported a different lamellated and hyperintense appearance of the synovium in infected joints, which can be differentiated from frond- like and hypertrophied synovium associated with particle-induced synovitis and from homogeneous fluid-signal intensity effusion associated with a nonspecific synovitis. MRI with metal artifact reduction technique has also been shown to detect osteolysis that is not visible on radiographs [96,97]. Contrast may provide additional benefit in detecting extracapsular spread of infection and abscess formation when compared to noncontrast MRI.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. MRI Knee Without IV Contrast MRI may have a role in the workup of periprosthetic infection. Advances in metal artifact reduction may expand the potential role of MRI. Using metal reduction techniques, Potter and Foo found that infected synovium has hyperintense laminar appearance, distinct from the appearance of particle disease [22,93]. They noted that, in selected cases, MRI may be helpful in detecting extracapsular spread of infection and abscess formation. Plodkowski et al [94] examined 28 patients with proven infected TKAs and 28 controls with noninfected TKA. They found a sensitivity of 86% to 92% and a specificity of 85% to 87%, with almost perfect interobserver agreement, when using the appearance of lamellated hyperintense synovitis to classify infected versus noninfected TKA. Li et al [95] also reported a different lamellated and hyperintense appearance of the synovium in infected joints, which can be differentiated from frond-like and hypertrophied synovium associated with particle-induced synovitis and from homogeneous fluid-signal intensity effusion associated with a nonspecific synovitis. MRI with metal artifact reduction technique has also been shown to detect osteolysis that is not visible on radiographs [96,97].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. US Knee US has a limited role in the workup of periprosthetic infection, but it can be readily used to assess soft tissues, including the presence of edema, hyperemia, and fluid collections about the knee joint in patients with TKA. This may be beneficial in certain situations (eg, practices that may perform fluoroscopy-guided aspiration).


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty injection of the radiolabeled WBCs [63]. Comparison of activity on the WBC image with activity on a bone scan (usually a 3-phase bone scan) has been advocated. A positive study for infection generally requires focal increased activity on the WBC study in the same location and distribution as the positive 3-phase bone scan [100]. Using a sequential combination of bone and In-111-labeled leukocyte scans in patients with loose or painful knee prostheses found a sensitivity of 88%, a specificity of 78%, a PPV of 75%, and an NPV of 90% for diagnosis of infection. They noted an area of potential utility for leukocyte scans, specifically that a negative indium leukocyte scan might support the absence of infection in otherwise equivocal cases and in situations in which a musculoskeletal pathologist is not available to interpret an intraoperative frozen section [100]. A small sample of indium scans in uncomplicated postoperative TKA patients has shown that inflammation can persist around the operative site in the absence of infection [100]. Bernard et al [50] reported a multicenter trial of various methods for diagnosing hip and knee infections. Scans using tagged WBCs or radiolabeled immunoglobulin demonstrated a sensitivity of 74% and a specificity of 76% for diagnosing infection. A literature review indicates sensitivities of 40% to 96% and specificities of 76% to 100% for WBC scans of joint prostheses [49,50,99-104]. Therefore, these studies are not useful as routine for differentiating mechanical failure from occult infection in painful loose total knee prostheses. Filippi and Schillaci [105] applied SPECT/CT using a hybrid camera to conventional planar Tc-99m-HMPAO- labeled leukocyte scintigraphy in patients with suspected infection. SPECT/CT was able to differentiate soft-tissue involvement from bone involvement. The authors argued that SPECT/CT might eliminate the necessity for a correlative bone scan with labeled leukocyte scans. WBC scans also have a decreased sensitivity with low-grade infection [66] and a limited neutrophilic component. Labeled leukocyte imaging may lead to a high false-positive rate because leukocytes accumulate in reactive bone marrow as well as in infection and it is not always possible to differentiate between the two [64,106].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. The addition of Tc-99m-labeled sulfur colloid bone marrow scanning has been investigated to reduce this confusion. Palestro et al [107] reported that sequential combined leukocyte/marrow imaging was 95% accurate for diagnosing prosthetic knee infection and was superior to bone scans alone or to bone scans in combination with labeled leukocyte imaging. Joseph et al [106] found that low sensitivity and the potential for false-negative results made this combination of scans of limited utility for diagnosing prosthetic infection, and therefore it is no longer used at their institution. In that group of 22 total knee prostheses evaluated and later operated upon, there was a sensitivity of 66%, a specificity of 100%, a PPV of 100%, an NPV of 88%, and an accuracy of 91%. Blanc et al [108] did a retrospective review of 168 patients. They determined Tc-99m-HMPAO labeled leucocyte scintigraphy was more sensitive for knee (84%) than hip prosthesis (57%) but was less specific for knee (52% versus 75%). The addition of blood-pool and flow scans was investigated to determine if hyperemia led to a match of bone marrow-labeled leukocyte uptake (and therefore a false-negative scan). These additional scans decreased the number of false- negative findings (sensitivity, 83%; specificity, 94%; PPV, 83%; NPV, 94%). Overall, the performance of the labeled leukocyte marrow scan protocol was nonetheless thought to be of limited clinical utility [106]. In contrast, Love et al [69] found the combination of In-111-labeled leukocyte/Tc-99m-labeled sulfur colloid marrow scanning to be the reference standard for diagnosing periprosthetic infection. The authors found the combination of labeled WBC and marrow scanning to be 100% sensitive and 100% specific for diagnosing infection in TKA [69]. Semiquantitative assessment of WBC scans using a combination of early and delayed imaging as a substitute for bone marrow imaging produced a >90% sensitivity and specificity in one series [99]. Love et al [109] examined 150 failed joint prostheses with histopathologic correlation and found that leukocyte/marrow imaging yielded a sensitivity of 96%, a specificity of 87%, and an accuracy of 91%. They found that leukocyte/marrow imaging was significantly more accurate than bone scan (50%), bone/gallium scan (66%), and leukocyte/bone imaging (70%) in their population.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. WBC scan and sulfur colloid scan may have a role in the workup of suspected infection in knee arthroplasty.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Variant 3: Pain after total knee arthroplasty. Infection excluded. Suspect aseptic loosening or osteolysis or instability. Additional imaging following radiographs. Imaging of rotational instability of a TKA is discussed in greater detail under Variant 5. If a patient has undergone a full workup and infection has been excluded, then loosening should be considered as the potential cause of knee pain and periprosthetic lucency. In multiple studies, aseptic loosening has been found to be a common cause of TKA failure [13,110-112]. Sharkey et al [13] found aseptic loosening to be the major cause of late stage (>2 years) TKA failure. Aseptic loosening may occur either because of inadequate primary fixation or because of failure after successful fixation. It is thought to result from mechanical stresses, osteolysis secondary to particle debris, or poor bone stock [21]. Loosening may be closely related to other forms of mechanical failure such as osteolysis,


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. instability, polyethylene liner wear, and periprosthetic fracture. Osteolysis is a leading cause of late TKA revision. Osteolysis, also known as particle disease and aggressive granulomatosis, occurs secondary to macrophage phagocytosis of particle debris. Debris originating from polyethylene, cement, and metal can all be causes of cell- mediated inflammatory response and osteolysis [113], but typically polyethylene is the most common cause. Areas of osteolysis contain granulation tissue with phagocytosed particulate debris [21]. The incidence of osteolysis is higher for cementless, compared with cemented TKA [114]. Osteolysis can occur anywhere but is more common in the region of the femoral condyles near the attachment of the collateral ligaments, along the periphery of the component, and along the access channels to the cancellous bone of the tibia, including screw holes [114,115]. Patients with osteolysis may be asymptomatic early on but can go on to develop pain, swelling, and acute synovitis.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Although small areas of osteolysis may be monitored, the presence of large areas of osteolysis suggest component loosening and may require revision surgery [116]. Imaging can also help evaluate available bone stock in preparation for revision surgery. Instability refers to abnormal and excessive displacement of the articular surfaces of the prosthesis [21]. Instability usually occurs because of surgical error and/or poor prosthesis selection and often results in revision surgery an average of 4 years after the primary arthroplasty [21]. Severe instability can result in dislocation. In a 2014 review of 781 cases of prosthesis failure, Sharkey et al [12] found that instability represented the third most common cause of prosthesis failure overall, accounting for 7.5% of all cases. The concepts of instability, malalignment, and loosening in TKA are closely interrelated [117]. When malalignment of the joint is created at the time of surgery, minor degrees of instability can become a significant problem. By the same token, instability, ongoing over time, can give rise to malalignment, which, in turn, can lead to loosening. Although ligamentous balance/imbalance plays a role in joint instability, it is not the only factor accounting for stability [118].


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. 3-Phase Bone Scan Knee There is insufficient evidence to support routine use of Tc-99m 3-phase bone scans for the assessment of instability.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Arthrography Knee CT joint arthrography can assess for lucency with contrast accumulation at the bone/cement/hardware interface. These areas of lucency are not specific for infection versus mechanical loosening.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. Imaging After Total Knee Arthroplasty CT Knee With IV Contrast CT with IV contrast is not useful for the assessment of aseptic loosening, osteolysis, or instability.


Imaging After Total Knee Arthroplasty

Imaging After Total Knee Arthroplasty. CT Knee Without and With IV Contrast CT without and with IV contrast is not useful for the assessment of aseptic loosening, osteolysis, or instability.