CAM 60106

Miscellaneous (Noncardiac, Nononcologic) Applications of Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography

Category:Radiology   Last Reviewed:February 2019
Department(s):Medical Affairs   Next Review:February 2020
Original Date:February 2013    

Description
Positron emission tomography (PET) images biochemical and physiologic functions by measuring concentrations of radioactive chemicals that are partially metabolized in the body region of interest. Radiopharmaceuticals used for PET are generated in a cyclotron or nuclear generator and introduced into the body by intravenous injection or by respiration.

For individuals who have epileptic seizures who are candidates for surgery who have fluorodeoxyglucose F 18 positron emission tomography (FDG-PET), the evidence includes 5 systematic reviews since the publication of 3 TEC Assessments. Relevant outcomes are symptoms, change in disease status, functional outcomes, health status measures, quality of life, hospitalizations, medication use and resource utilization. The TEC Assessment and Program in Evidence-based Care PET recommendation report both concluded that FDG-PET accurately localizes the seizure focus compared to appropriate reference standards. A recent systematic review suggested it was difficult to discern the incremental value of FDG-PET in patients who have foci well localized by ictal scalp electroencephalography and magnetic resonance imaging. The evidence on whether FDG-PET has a predictive value for a good surgical outcome is mixed. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome.

For individuals who have suspected osteomyelitis who receive FDG-PET, the evidence includes 2 meta-analyses. Relevant outcomes are test accuracy and validity, other test performance measures, change in disease status, functional outcomes, quality of life and hospitalizations. One systematic review and meta-analysis of 9 studies showed FDG-PET and FDG-PET plus CT were useful for diagnosing suspected osteomyelitis in the feet of patients with diabetes. The results of the second meta-analysis showed FDG-PET was the most accurate mode (pooled sensitivity, 96%; 95% confidence interval [CI], 88% to 99%; pooled specificity, 91%; 95% CI, 81% to 95%) for diagnosing chronic osteomyelitis. The results appear to be robust across fairly diverse clinical populations, which strengthens the conclusions. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome.

For individuals who have suspected Alzheimer's disease (AD) who receive FDG-PET, the evidence includes 5 systematic reviews of observational studies. Relevant outcomes are test accuracy and validity, other test performance measures, symptoms, quality of life and hospitalizations. The studies included in the reviews were generally of poor quality. There is no standard cutoff for PET positivity for diagnosing AD, and many studies have not included postmortem confirmation of AD as the reference standard, leading to uncertainty about estimates of performance characteristics. FDG-PET may have high sensitivity and specificity for diagnosing AD, but there is little evidence comparing the performance characteristics of clinical diagnosis with PET to clinical diagnosis without PET, so the incremental value of adding PET to the standard clinical diagnosis is unclear. No studies have reported on clinical outcomes of patients diagnosed with versus those without FDG-PET. The evidence is insufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have suspected large vessel vasculitis who receive FDG-PET, the evidence includes 5 systematic reviews of observational studies. Relevant outcomes are test accuracy and validity, other test performance measures, symptoms, morbid events, quality of life, hospitalizations and treatment-related morbidity. Most studies included in the reviews were small and lacked controls. The reported performance characteristics were heterogeneous, but reviewers were unable to determine the source of heterogeneity. Studies comparing PET to the true reference standard of biopsy or angiography were rare. There are no consensus criteria to define the presence of vascular inflammation by FDG-PET in large vessel vasculitis, and different parameters with visual and semiquantitative methods have been reported. Studies demonstrating changes in management based on PET results or improvements in clinical outcomes are lacking. The evidence is insufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have diverse noncardiac or nononcologic conditions (e.g., central nervous system, pulmonary and musculoskeletal diseases) who receive FDG-PET, the evidence includes a few systematic reviews. Relevant outcomes are overall survival, symptoms, change in disease status, functional outcomes, health status measures, quality of life, hospitalizations, medication use and resource utilization. Many studies cited in the reviews were small, retrospective and published in the 1990s to early 2000s; many did not directly compare 1 modality with another in the same patient group or connect the PET results in individual patients to improved clinical outcomes. Studies are needed that demonstrate FDG-PET results will change management that improves patient outcomes to determine that it is a clinically useful test. The evidence is insufficient to determine the effect of the technology on health outcomes.

Background 
Positron emission tomography (PET) scans are based on the use of positron emitting radionuclide tracers coupled to other molecules, such as glucose, ammonia or water. The radionuclide tracers simultaneously emit 2 high-energy photons in opposite directions that can be simultaneously detected (referred to as coincidence detection) by a PET scanner, which comprises multiple stationary detectors that encircle the region of interest.

A variety of tracers are used for PET scanning, including oxygen 15, nitrogen 13, carbon 11 and fluorine 18 (F 18). The radiotracer most commonly used in oncology imaging has been F 18, coupled with deoxyglucose (FDG), which has a metabolism related to glucose metabolism. While FDG has traditionally been used in cancer imaging, it potentially has many other applications.

Epilepsy
Approximately one-third of patients with epilepsy do not achieve adequate seizure control with antiepileptic drugs.1 Individuals with intractable epilepsy are candidates for other treatments, such as epilepsy surgery. Many effective surgical procedures are available, and the treatment selected depends on characteristics of the seizures (e.g., the epileptogenic zone) and the extent to which it can be resected safely. Neuroimaging techniques, such as magnetic resonance imaging (MRI), electroencephalography (EEG), PET, single-photon emission computed tomography (SPECT), electric (ESI) and magnetic source imaging (MSI) and magnetic resonance spectroscopy (MRS), have been used to locate the epileptic focus, thereby helping to guide the operative strategy. Some patients with epilepsy will have no identifiable MRI abnormality to help identify the focal region. PET, particularly using fluorodeoxyglucose F 18 (FDG), is a neuroimaging technique frequently used in patients being considered for surgery. FDG-PET produces an image of distribution of glucose uptake in the brain, presumably detecting focal areas of decreased metabolism.2 PET may be able to correctly identify the focus in patients with unclear or unremarkable MRI results or discordant MRI and EEG results that could reduce the need for invasive EEG. PET scanning may also help to predict which patients will have a favorable outcome following surgery. The Engel classification system is often used to describe the surgical outcome: class I: seizure free or free of disabling seizures; class II: almost seizure free; class III: worthwhile improvement; and class IV: no worthwhile improvement. 

Suspected Chronic Osteomyelitis
Diabetic foot infections cause substantial morbidity and are a frequent cause of lower-extremity amputations. Foot infections can spread to contiguous deep tissues, including the bone. Diagnosis of osteomyelitis is challenging. The reference standard for diagnosis is examination of bacteria from a bone biopsy along with histologic findings of inflammation and osteonecrosis. In an open wound, another potential test for osteomyelitis is probe-to-bone test, which involves exploring the wound for palpable bone with a sterile blunt metal probe.4 Plain radiographs are often used as screening tests before biopsy but they tend to have low specificity especially in early infection. When radiographs are inconclusive, a more sophisticated imaging technique can be used. Both MRI and computed tomography have high sensitivity for diagnosis of osteomyelitis,5 but cannot be used in patients with metal hardware. FDG-PET has high resolution that should be an advantage for accurate localization of leukocyte accumulation and can be used when MRI is not possible or inconclusive. In addition, PET semiquantitative analysis could facilitate the differentiation of osteomyelitis from noninfectious conditions such as neuropathic joint.  

Suspected Alzheimer's Disease
Definitive diagnosis of Alzheimer's disease (AD) requires histopathologic examination of brain tissue obtained by biopsy or autopsy. In practice, clinical criteria based on clinical examination, neurological and neuropsychological examinations and interviews with informants (e.g., family members or caregivers) are used to diagnose AD by excluding other diseases that can cause similar symptoms, and to distinguish AD from other forms of dementia. There are currently no cures or preventive therapies for AD. Early diagnosis might facilitate early treatment of cognitive, behavioral and psychiatric symptoms that could perhaps delay functional deficits and improve quality of life. Early diagnosis may be crucial in the future if other therapies become available to treat or slow progression of disease. FDG-PET can demonstrate reduction in glucose metabolism associated with dementia. These changes in metabolism are detectable years before the onset of clinical symptoms.6 The changes typically have a characteristic pattern of hypometabolism that could be useful not only in distinguishing AD from normal aging but also from other dementias, psychiatric disorders and cerebrovascular diseases.7-9  

Large Vessel Vasculitis
Large vessel vasculitis causes granulomatous inflammation primarily of the aorta and its major branches.10 There are 2 major types of large vessel vasculitis: giant cell arteritis (GCA) and Takayasu arteritis (TA). Classification criteria for CGA and TA were developed by American College of Rheumatology in 1990.11,12 The definitions have since been refined by the 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides.13 Biopsy and angiography are considered the criterion standard techniques for diagnosis but they are invasive and detect changes that occur late in disease. In practice, the diagnosis is challenging because patients tend to have nonspecific symptoms such as fatigue, loss of appetite, weight loss and low grade fever, as well as nonspecific lab findings such as increased C-reactive protein or erythrocyte sedimentation rate.14 Misdiagnosis is common, particularly in the early stages of disease. Unfortunately, late diagnosis can lead to serious aortic complications and death. Since activated inflammatory cells accumulate glucose, FDG-PET may be able to detect and visualize early inflammation in vessel walls and facilitate early diagnosis, thereby allowing treatment with glucocorticoids before irreversible arterial damage has occurred.

This evidence review only addresses the use of radiotracers detected with the use of dedicated full-ring PET scanners. Radiotracers such as FDG may be detected using SPECT cameras, a hybrid PET/SPECT procedure that may be referred to as FDG-SPECT or molecular coincidence detection. The use of SPECT cameras for PET radiotracers presents unique issues of diagnostic performance and is not considered herein.

Regulatory Status 
Following the U.S. Food and Drug Administration’s (FDA) approval of the Penn-PET in 1989, a number of PET scan platforms have been cleared by FDA through the 510(k) process. These systems are intended to aid in detecting, localizing, diagnosing, staging and restaging of lesions, tumors, disease and organ function for the evaluation of diseases, and disorders such as, but not limited to, cardiovascular disease, neurologic disorders, and cancer. The images produced by the system can aid in radiotherapy treatment planning and interventional radiology procedures.

PET radiopharmaceuticals have been evaluated and approved as drugs by FDA for use as diagnostic imaging agents. These radiopharmaceuticals are approved for specific conditions. 

In December 2009, FDA issued guidance for Current Good Manufacturing Practice for PET drug manufacturers15 and, in August 2011, issued similar Current Good Manufacturing Practice guidance for small businesses compounding radiopharmaceuticals.16 An additional final guidance document, issued in December 2012, required all PET drug manufacturers and compounders to operate under an approved new drug application (NDA) or abbreviated NDA, or investigational new drug application, by December 12, 2015.17 

In 1994, the FDG radiotracer was originally approved by FDA through the NDA (20-306) process. The original indication was for "the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures". Added indications in 2000 were for "Assessment of glucose metabolism to assist in the evaluation of malignancy…" and "Assessment of patients with coronary artery disease and left ventricular dysfunction….". (Note that many manufacturers have NDAs for FDG.)18  

Multiple manufacturers have approved NDAs for FDG. 

See related evidence reviews 60126 and 60151 for oncologic indications and 60120 for cardiac indications for FDG. 

Relative Policies
60120 Cardiac Applications of PET Scanning
60126 Oncologic Applications of PET Scanning
60151 PET Scanning in Oncology to Detect Early Response during Treatment
60155 Beta Amyloid Imaging with Positron Emission Tomography (PET) for Alzheimer’s Disease

Policy
Positron emission tomography (PET) using 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) may be considered MEDICALLY NECESSARY in:

  1. The assessment of selected patients with epileptic seizures who are candidates for surgery (see Policy Guidelines).
  2. The diagnosis of chronic osteomyelitis.

The use of FDG- PET for all other miscellaneous indications is INVESTIGATIONAL, including, but not limited to:

CNS Diseases

  • Autoimmune disorders with CNS manifestations, including:
    • Behçet's syndrome
    • lupus erythematosus
  • Cerebrovascular diseases, including:
    • arterial occlusive disease (arteriosclerosis, atherosclerosis)
    • carotid artery disease
    • cerebral aneurysm
    • cerebrovascular malformations (AVM and Moya Moya disease)
    • hemorrhage
    • infarct
    • ischemia
  • Degenerative motor neuron diseases, including:
    • amyotrophic lateral sclerosis
    • Friedreich's ataxia
    • olivopontocerebellar atrophy
    • Parkinson's disease
    • progressive supranuclear palsy
    • Shy-Drager syndrome
    • spinocerebellar degeneration
    • Steele-Richardson-Olszewski disease
    • Tourette's syndrome
  • Dementias, including:
    • Alzheimer's disease
    • multi-infarct dementia
    • Pick's disease
    • frontotemporal dementia
    • dementia with Lewy-Bodies
    • presenile dementia
  • Demyelinating diseases, such as multiple sclerosis
  • Developmental, congenital or inherited disorders, including:
    • adrenoleukodystrophy
    • Down syndrome
    • Huntington’s chorea
    • kinky-hair disease (Menkes’ syndrome)
    • Sturge-Weber syndrome (encephalofacial angiomatosis) and the phakomatoses
  • Miscellaneous
    • chronic fatigue syndrome
    • sick building syndrome
    • post-traumatic stress disorder
  • Nutritional or metabolic diseases and disorders, including:
    • acanthocytes
    • hepatic encephalopathy
    • hepatolenticular degeneration
    • metachromatic leukodystrophy
    • mitochondrial disease
    • subacute necrotizing encephalomyelopathy
  • Psychiatric diseases and disorders, including:
    • affective disorders
    • depression
    • obsessive-compulsive disorder
    • psychomotor disorders
    • schizophrenia
  • Pyogenic infections, including:
    • aspergillosis
    • encephalitis
  • Substance abuse, including the CNS effects of alcohol, cocaine and heroin
  • Trauma, including brain injury and carbon monoxide poisoning
  • Viral infections, including:
    • acquired immune deficiency syndrome (AIDS)
    • AIDS dementia complex
    • Creutzfeldt-Jakob syndrome
    • progressive multifocal leukoencephalopathy
    • progressive rubella encephalopathy
    • subacute sclerosing panencephalitis
  • Mycobacterium infection
  • Migraine
  • Anorexia nervosa
  • Cerebral blood flow in newborns
  • Vegetative versus "locked-in" state

Pulmonary Diseases

  • Adult respiratory distress syndrome
  • Diffuse panbronchiolitis
  • Emphysema
  • Obstructive lung disease
  • Pneumonia

Musculoskeletal Diseases

  • Spondylodiscitis
  • Joint replacement follow-up

Other

  • Giant cell arteritis
  • Vasculitis
  • Inflammatory bowel disease
  • Sarcoidosis
  • Fever of unknown origin
  • Inflammation of unknown origin

Policy Guidelines
In patients with epileptic seizures, appropriate candidates are patients with complex partial seizures that have failed to respond to medical therapy and who have been advised to have a resection of a suspected epileptogenic focus located in a region of the brain accessible to surgery. Conventional techniques for seizure localization must have been tried and provide data that suggested a seizure focus but were not sufficiently conclusive to permit surgery. In addition, the purpose of the PET examination should be to avoid subjecting the patient to extended preoperative electroencephalographic recording with implanted electrodes or to help localize and minimize the number of sites for implanted electrodes to reduce the morbidity of that procedure.

Coding Issues
A PET scan essentially involves 3 separate activities: (1) Manufacture of the radiopharmaceutical, which may be manufactured on site, or manufactured at a regional delivery center with delivery to the institution performing PET; (2) actual performance of the PET scan; and (3) interpretation of the results. The following CPT codes may be used.

CPT Codes:
78608: Brain imaging, positron emission tomography (PET); metabolic evaluation
78609: Brain imaging, positron emission tomography (PET); perfusion evaluation
78811: Positron emission tomography (PET) imaging; limited area (e.g., chest, head/neck)
78812: Positron emission tomography (PET) imaging; skull base to mid-thigh
78813: Positron emission tomography (PET) imaging; whole body
78814: Positron emission tomography (PET) imaging with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; limited area (e.g., chest, head/neck)
78815: Positron emission tomography (PET) imaging with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; skull base to mid-thigh
78816: Positron emission tomography (PET) imaging with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; whole body

There are HCPCS codes specific to the following radiotracers:

A9526: Nitrogen N-13 ammonia, diagnostic, per study dose, up to 40 millicuries
A9552: Fluorodeoxyglucose F-18 FDG, diagnostic, per study dose, up to 45 millicuries
A9580: Sodium fluoride F-18, diagnostic, per study dose, up to 30 millicuries

Benefit Application
BlueCard®/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and, thus, these devices may be assessed only on the basis of their medical necessity.

Rationale
Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition. 

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources. 

fluorine 18 fluorodeoxyglucose positron emission tomography Clinical Context and Test Purpose
The purpose of fluorine 18 fluorodeoxyglucose PET (FDG-PET) in patients with epilepsy, chronic osteomyelitis, suspected Alzheimer disease (AD), suspected large vessel vasculitis (LVV), or other noncardiac or nononcologic conditions is to confirm a diagnosis or to inform the decision on selecting treatment regimens. 

The question addressed in this evidence review is: Does the use of FDG-PET improve the net health outcome in individuals with epilepsy, chronic osteomyelitis, suspected AD, suspected LVV, or other noncardiac or nononcologic conditions? 

The following PICOTS were used to select literature to inform this review. 

Patients 
The populations of interest include patients with epilepsy, chronic osteomyelitis, suspected AD, suspected LVV, or other noncardiac or nononcologic conditions (eg, central nervous system, pulmonary, and musculoskeletal diseases).

Interventions
The intervention of interest is  FDG-PET. 

Comparators
The following tests and practices are currently being used to make decisions about managing the following indications:

  • For epilepsy, ictal scalp electroencephalography and magnetic resonance imaging (MRI).
  • For suspected chronic osteomyelitis, computed tomography (CT), radiography, technetium 99 bone scintigraphy, leukocyte scintigraphy, and MRI.
  • For suspected AD, clinical diagnosis without FDG-PET.
  • For suspected LVV, clinical diagnosis without FDG-PET.
  • For diverse noncardiac or nononcologic conditions, CT, radiograph, and MRI. 

Outcomes 
For patients with epilepsy, 2 outcomes of interest are: (1) to identify the epileptic focus accurately before surgery and (2) to predict which patients will have a favorable outcome following  surgery. 

For patients with suspected AD, suspected chronic osteomyelitis, and suspected LVV, or other noncardiac or nononcologic conditions, outcomes of interest include disease-related morbidity and  mortality. 

Timing 
For patients with epilepsy, FDG-PET would be conducted prior to   surgery. 

For patients with suspected AD, suspected chronic osteomyelitis, suspected LVV, or other noncardiac or nononcologic conditions, FDG-PET would be performed following inconclusive clinical examinations and standard   radiographs. 

Setting
FDG-PET is administered in an imaging center equipped with a PET scanner. 

Epilepsy
Technically  Reliable
Assessment of technical reliability focuses on specific tests and operators and requires review of unpublished and often proprietary information. Review of specific  tests, operators, and unpublished data are outside the scope of this evidence review and alternative sources exist. This evidence review focuses on the clinical validity and clinical utility. 

Clinically Valid 
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse). 

Systematic Reviews 
A TEC Assessment (1996) reviewed the evidence on the use of PET in individuals with seizure disorders from 12 studies in which the results of PET scans were  correlated with results of an appropriate reference standard test.19, The highest quality blinded study (N=143) reported that PET correctly localized the seizure focus in 60% of patients, incorrectly localized it in 6%, and was inconclusive in 34%. Reviewers concluded that because localization can be improved with PET, selection of surgical candidates is improved and, therefore, PET for assessing patients who have medically refractory complex partial seizures and are potential candidates for surgery met TEC criteria. All other uses of PET for the management of seizure disorders did not meet the TEC criteria. Tables 1 and 2 summarize the characteristics and results of several meta-analyses of FDG-PET published since that TEC Assessment that have assessed either presurgical planning of patients who are candidates for epilepsy surgery or prediction of surgical outcomes. A brief discussion of each trial follows.

Table 1. Characteristics of Systematic Reviews Assessing Use of FGD-PET for Epilepsy

Study Dates Trials N (Range) Design Outcomes
Jones et al (2016)22 1946-2014 27 3163 (25-434) OBS Prognostic accuracy
Wang et al (2016)23 2000-2015 18 391 (5-86) NR Prognostic accuracy
Burneo et al (2015)24 1946-2013 39 2650 OBS Diagnotic/prognostic accuracy, clinical utility
Englot et al (2012)25 1990-2010 21a 1,199 (13-253)a OBS Prognostic accuracy
Willmann et al (2007)26 1992-2006 46 1112 (2-117) OBS Prognostic accuracy

FDG-PET: fluorine 18 fluorodeoxyglucose positron emission tomography; OBS: observational.
a Total number of studies and participants included; unclear if all studies included PET as a predictor.  

Jones et al (2016) published a systematic review of neuroimaging for surgical treatment of temporal lobe epilepsy.22, Inclusion criteria were systematic reviews, randomized controlled trials (RCTs), or observational studies (with >20 patients and at least 1-year follow-up) of neuroimaging in the surgical evaluation for temporal lobe epilepsy. Reviewers searched EMBASE, MEDLINE, and Cochrane databases. Twenty-seven studies with 3163 patients were included in the review, of which 11 observational studies with 1358 patients evaluated FDG-PET. Good surgical outcome was defined as Engel classes I and II. Meta-analysis was not performed. Results are summarized in Table 2. 

Wang et al (2016) conducted a systematic review of prognostic factors for seizure outcomes in patients with MRI-negative temporal lobe epilepsy included a search of MEDLINE.23 Eighteen studies (total N=391 patients) were included with a mean or median follow-up of more than 1 year. Seizure freedom was defined as freedom   from any type of seizure or an Engel class I seizure outcome. Odds ratios and corresponding 95% confidence intervals (CIs) were calculated to compare the pooled proportions of seizure freedom between the groups who had localization of hypometabolism in the resected lobe vs those who did not. Table 2 shows the summary  results. 

Burneo et al (2015) published a recommendation report for the Program in Evidence-based Care and the PET steering committee of Cancer Care Ontario, which was  based on a systematic review of studies of diagnostic accuracy and clinical utility of FDG-PET in the presurgical evaluation of adult and pediatric patients with medically intractable epilepsy.24, The literature review included searches of the MEDLINE, EMBASE, OVID, and Cochrane databases. Systematic reviews, RCTs, and observational studies that evaluated the use of FDG-PET in medically intractable epilepsy were eligible for inclusion. Reviewers included 39 observational studies (total N=2650 participants) in the qualitative review. Good surgical outcome was defined as Engel class I, II, or III, seizure-free, or significant improvement (<10 seizures per year and at least a 90% reduction in seizures from the preoperative year). Due to heterogeneity in patient populations, study designs, outcome measurements, and methods of PET interpretation, pooled estimates were not provided; ranges are provided in Table 2. 

Englot et al (2012) performed a systematic review of predictors of long-term seizure freedom after surgery for frontal lobe epilepsy; they included articles found through a MEDLINE search that had at least 10 participants and 48 months of follow-up.25, Long-term seizure freedom was defined as Engel class I outcome. Twenty- one studies (total N=1199 patients) were included; the number of studies that specifically addressed PET was not specified. Results are summarized in Table 2. Reviewers found that PET scans did not predict seizure   freedom. 

Willmann et al (2007) conducted a meta-analysis on the use of FDG-PET for preoperative evaluation of adults with temporal lobe epilepsy included 46 studies published identified through a MEDLINE search.26, Follow-up ranged from 3 to 144 months. Engel class I and II were defined as a good surgical outcome. The  prognostic positive predictive value (PPV) for ipsilateral PET hypometabolism was calculated, but the reviewers noted significant variation in study designs and lack of precise data. Reviewers found that ipsilateral PET hypometabolism had a predictive value for a good outcome of 86% (see Table 2). The incremental benefit of PET was unclear. 

Table 2. Results of Systematic Reviews on Use of FDG-PET for Epilepsy

Study Studies N Outcomes Estimate or Range 95% CI  /2 p
Jones et al  (2016)22 11 1358 Surgical outcome
  • No overall summary given
  • Reported conflicting findings on prognostic importance of PET-identified focal hypometabolism
No Pooling    
Wang al et  (2016)23 5 NR Surgical outcome (freedom from seizures)
  • OR for PET hypometabolism positive vs negative, 2.11
0.95 to 4.65 0 0.06
Burneo et al  (2015)24 8 310 Percent agreement, localization with PET vs EEG
  • 56%-90% overall (adults)
  • 63%-90% in temporal lobe epilepsy (adults)
No pooling    
  13 1064 Prognostic accuracy (good surgical outcome)
  •  36%-89% (adults)
No pooling    
  6 690 Clinical decisions (influence decision making)
  • 53%-71% (adults)
  • 51%-95% (children)
No pooling    
Englot et al  (2012)25 21a 1199a Prognostic accuracy (good surgical outcome) % for PET focal vs PET nonfocal, 52% vs 48% NR NR 0.61
Willmann et al  (2007)26 46 1112 Prognostic accuracy (good surgical outcome)
  • PPV=86%
NR                 NR NR

CI: confidence interval; EEG: electroencephalography; FDG: fluorine 18 fluorodeoxyglucose; NR: not reported; OR: odds ratio; PET: positron emission tomography; PPV: positive predictive value.
a Total number of studies and participants included; unclear if all studies included PET as a predictor.

Observational  Studies 
In a study published after the most recent systematic reviews, Traub-Weidinger et al (2016) reviewed a database of pediatric patients with epilepsy who underwent hemispherotomy and were evaluated with both FDG-PET and MRI before surgery (N=35).27, Identifying the hemisphere harboring the epileptogenic zone before    surgery has been shown to improve surgical outcomes. Seizure outcomes were measured using International League Against Epilepsy classifications. At 12 months postsurgery, 100% of patients with unilateral FDG-PET hypometabolism were seizure-free, while 95% of patients with unilateral lesions identified by MRI were seizure-free. For patients with bilateral FDG-PET hypometabolism, 75% were seizure-free at 12 months, while 71% of patients with bilateral lesions identified by MRI were seizure-free. 

Clinically Useful 
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing. 

Direct Evidence 
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from   RCTs. 

The recommendation report by Burneo et al (2015) discussed 3 retrospective studies demonstrating the impact of FDG-PET on clinical management of adults with epilepsy and 3 retrospective studies on change in clinical management based on FDG-PET results in children with epilepsy.24, After receiving FDG-PET results on adults, some clinicians changed surgical decisions, used the results to guide intracranial electroencephalography, and ruled out an additional evaluation of the patient. Among pediatric patients who underwent FDG-PET, clinicians reported using the results to alter surgical decisions, classify symptomatic infantile spasms, and avoid invasive monitoring due to localizing information. The study results were not pooled due to heterogeneity among the study designs and patient populations. 

Section Summary: Epilepsy 
The TEC Assessment and the Program in Evidence-based Care recommendations summarized evidence on the use of PET to localize seizure foci for presurgical evaluation. Although data were exclusively from observational studies and the results were heterogeneous, the findings generally supported the use of PET for presurgical evaluation of adult and pediatric patients with intractable epilepsy to localize foci. For predicting which patients would have a favorable surgery outcome, the data on PET were mixed but supported a possible moderate relation between PET findings and prognosis. There are several retrospective studies that surveyed clinicians on the utility of FDG-PET in managing patients with epilepsy. In general, the clinicians reported that the information from FDG-PET was helpful in surgical management decisions. Only observational studies are available, most having small samples sizes with varying patient characteristics and definitions of good surgical outcomes. 

Suspected Chronic Osteomyelitis Technically Reliable
Assessment of technical reliability focuses on specific tests and operators and requires review of unpublished and often proprietary information. Review of specific  tests, operators, and unpublished data are outside the scope of this evidence review and alternative sources exist. This evidence review focuses on the clinical validity and clinical utility. 

Clinically Valid 
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse). 

Systematic Reviews 
Lauri et al (2017) published a systematic review of 27 trials of diabetic patients with suspicion of osteomyelitis of the foot that compared the diagnostic performance of several imaging techniques.28, MRI, technetium 99m hexamethylpropyleneamineoxime white blood cell (WBC) scan, indium In 111 oxyquinoline WBC scan, or FDG-PET plus CT were assessed. In this population, the sensitivity and specificity of FDG-PET/CT (6 studies; 254 patients) were 89% (95% CI, 68% to 97%) and   92% (95% CI, 85% to 96%), respectively. The diagnostic odds ratio for FDG-PET was 95, and the positive and negative likelihood ratios were 11 and 0.11, respectively. Of the 4 modalities included, FDG-PET/CT and technetium 99m hexamethylpropyleneamineoxime WBC scans had greater specificity (both 92%) than MRI or In-oxine WBC scans (both 75%). Sensitivity did not differ significantly between modalities: 93% for MRI, 92% for indium In 111 oxyquinoline WBC, 91%   for technetium 99m hexamethylpropyleneamineoxime WBC, and 89% for FDG-PET. The review was limited by the small size of studies included, which precluded subgroup or meta-regression  analyses. 

A systematic review by Treglis et al (2013) assessed 9 studies (total N=299 patients), FDG-PET and PET with CT were found to be useful for assessing suspected osteomyelitis in the foot of patients with diabetes.29, A meta-analysis of 4 studies found a sensitivity of 74% (95% CI, 60% to 85%), a specificity of 91% (95% CI, 85% to 96%), a positive likelihood ratio of 5.56 (95% CI, 2.02 to 15.27), a negative likelihood ratio of 0.37 (95% CI, 0.10 to 1.35), and a diagnostic odds ratio of 16.96 (95% CI, 2.06 to 139.66). The summary area under the receiver operating characteristic curve was 0.874. 

Termaat et al (2005) conducted a systematic review of diagnostic imaging to assess chronic osteomyelitis.30 Reviewers assessed 6 imaging approaches to chronic osteomyelitis, including FDG-PET, and concluded that PET was the most accurate mode (pooled sensitivity, 96%; 95% CI, 88% to 99%; pooled specificity, 91%; 95%  CI, 81% to 95%) for diagnosing chronic osteomyelitis, including leukocyte scintigraphy was adequate in the peripheral skeleton (sensitivity, 84%; 95% CI, 72% to 91%; specificity, 80%; 95% CI, 61% to 91%) but was inferior in the axial skeleton (sensitivity, 21%; 95% CI, 11% to 38%; specificity, 60%; 95% CI, 39% to 78%). The assessment of PET was based on 4 prospective, European studies published between 1998 and 2003 (total N=1660 patients). However, the study populations varied and included the following: (1) 57 patients with suspected spinal infection referred for FDG-PET and who had previous spinal surgery but not "recently"31; (2) 22 trauma patients scheduled for surgery who had suspected metallic implant-associated infection32; (3) 51 patients with recurrent osteomyelitis or  osteomyelitis symptoms for more than 6 weeks, 36 in the peripheral skeleton and 15 in the central skeleton33; and (4) 30 consecutive nondiabetic patients referred for possible chronic osteomyelitis.34, The results appeared to be robust across fairly diverse clinical populations, which strengthen the conclusions.

Prospective Studies 
Rastogi et al (2016) published a study comparing the efficacy of FDG-PET plus CT with contrast-enhanced MRI in the detection of diabetic foot osteomyelitis in  patients with Charcot neuroarthropathy.35, Patients with suspected diabetic foot osteomyelitis (N=23) underwent radiographs, FDG-PET/CT, and contrast-enhanced  MRI. Bone culture, which is considered the criterion standard, identified 12 of the 23 patients with osteomyelitis. The sensitivity, specificity, PPV, and negative predictive value (NPV) of FDG-PET/CT in diagnosing osteomyelitis were 83%, 100%, 100%, and 85%, respectively. The same measures for contrast-enhanced MRI were 83%, 64%, 71%, and 78%,  respectively. 

Clinically Useful 
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing. 

Direct Evidence 
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. 

No RCTs identified assessed the evidence on the clinical utility of FDG-PET for diagnosing osteomyelitis. 

Chain of Evidence 
Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility. 

Diagnosing osteomyelitis is challenging and FDG-PET may provide additional information along the diagnostic pathway. Currently, bone biopsy is considered the reference standard, and radiographs are often used as screening tests prior to bone biopsy. When radiographs are inconclusive, other imaging techniques have been used, such as MRI and CT. While MRI has been shown to have a high sensitivity in diagnosing osteomyelitis, FDG-PET has also been shown to have high sensitivity and can be used when MRI is inconclusive or not possible (eg, patients with metal hardware). 

Section Summary: Suspected Chronic Osteomyelitis 
Evidence for the use of FDG-PET to diagnose chronic osteomyelitis includes 3 systematic reviews and a prospective study published after the systematic reviews. FDG-PET and FDG-PET/CT were found to have high specificity and PPVs in diagnosing osteomyelitis. Compared with other modalities, FDG-PET and FDG- PET/CT were found to have better diagnostic capabilities than contrast-enhanced MRI and leukocyte scintigraphy. 

Suspected Alzheimer Disease 
This evidence review does not discuss PET tracers that bind to amyloid beta plaques (see review 60155). 

Technically  Reliable 
Assessment of technical reliability focuses on specific tests and operators and requires review of unpublished and often proprietary information. Review of specific  tests, operators, and unpublished data are outside the scope of this evidence review and alternative sources exist. This evidence review focuses on the clinical validity and clinical utility. 

Clinically Valid 
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse). 

Systematic Reviews 
Summaries of the characteristics and results of several meta-analyses of the early diagnosis of AD in people with cognitive impairment or for differentiating between potential causes of dementia are shown in Tables 3 and 4 and are briefly described below. 

Table 3. Characteristics of Systematic Reviews on Use Assessing FDG-PET for AD and Dementia

Study Dates Studies N (Range) Design Outcome
Smailagic et al (2015)36 1999-2013 16 697 (19-94) OBS  Diagnostic accuracy for predicting conversion from MDI to AD
Davison et al  (2014)37              Up to 2013 8 197 (7-199)  OBS  Diagnostic accuracy for diagnosis of AD, differential diagnosis in dementia, predicting conversion from MCI to AD 
Bloudek et al  (2011)38 1990-2010 119 NR OBS  Diagnostic accuracy for diagnosis of AD, differential diagnosis in dementia 
Yuan et al  (20019)38 2001-2005 6 280 (17-128)  OBS  Diagnostic accuracy for predicting conversion to AD in those with MCI 
Matchar et al  (2001)40 1995-2001    18 1018 (10-138)  OBS  Diagnostic accuracy for distinguishing AD from healthy controls and for differential diagnosis in dementia 

AD: Alzheimer disease; FDG-PET: fluorine 18 fluorodeoxyglucose positron emmission tomograpy; MCI: mild cognitive impairment; NR: not reported; OBS: observational 

Smailagic et al (2015) conducted a Cochrane review to assess the diagnostic accuracy of FDG-PET for detecting people who clinically convert to AD or other forms of dementia at follow-up.36, Included studies evaluated the diagnostic accuracy of FDG-PET to determine the conversion from mild cognitive impairment (MCI) to AD or to other forms of dementia. Sixteen studies (total N=697 participants) were included in the qualitative review and 14 studies (n=421 participants) were included in the analysis. Because there are no accepted thresholds to define positive findings based on PET scans and studies used mixed thresholds for diagnosis, reviewers used a hierarchical summary receiver operating characteristic curve to derive pooled estimates of performance characteristics at fixed values. Results are shown in Table 4. Five studies evaluated the accuracy of FDG-PET for all types of dementia. The sensitivities ranged between 46% and 95% while the specificities between 29% and 00%; however, a meta-analysis could not be conducted because of the small number of studies sample sizes. Reviewers indicated that most studies were poorly reported and had an unclear risk of bias, mainly for the reference standard and participant selection domains. 

In a systematic review (quality assessment of included studies was not reported), Davison et al (2014) reported on studies on the diagnostic performance of FDG-PET  and single-photon emission computed tomography identified through MEDLINE.37, Three studies (197 patients) used histopathology as the reference standard. In  patients with or without a clinical diagnosis of AD, sensitivity was 84% and specificity was 74%; in patients with memory loss or dementia, sensitivity was 94% and specificity was approximately 70%; in patients undergoing evaluation for dementia, sensitivity was 94% and specificity was 73%. Precision estimates were not given. In 3 different studies (271 participants), the sensitivities and specificities of FDG-PET for distinguishing AD from Lewy body dementia ranged from 83% to 99% and from 71% to 93%, respectively. And in 2 studies (183 participants), for predicting conversion from MCI to AD, sensitivity and specificity of PET ranged from 57% to 82% and from 67% to 78%,  respectively. 

Bloudek et al (2011) assessed diagnostic strategies for AD in a meta-analysis.38, Reviewers included 119 studies of diagnostic performance characteristics published from 1990 to 2010. Studies were identified through a search of MEDLINE and included imaging, biomarkers, and clinical diagnostic strategies. Twenty studies  included performance characteristics of FDG-PET for diagnosing AD compared with normal, nondemented controls. Thirteen studies described characteristics of FDG-PET for diagnosing AD compared with demented controls. FDG-PET demonstrated the highest area under the receiver operating characteristic curve, sensitivity, and specificity among all of the diagnostic methods for distinguishing AD from normal controls but one of the lowest receiver operating characteristic comparing AD with non-AD demented controls (excluding MCI), due primarily to the low specificity in this group. Results are shown in Table 4. 

In a meta-analysis, Yuan et al (2009) compared the prognostic capacity of FDG-PET, single-photon emission computed tomography, and structural MRI to predict patients’ conversion from MCI to AD.39 Using 24 articles (total N=1112 patients) published between 1990 to 2008 (6 studies with 280 patients on FDG-PET, published 2001-2005), reviewers found no statistically significant difference among the 3 modalities in pooled sensitivity, pooled specificity, or negative likelihood ratio. Results are shown in Table 4. There was strong evidence of between-study heterogeneity and marked asymmetry in the funnel plot (with studies missing from the bottom left quadrant), indicating possible publication bias of studies with null results. Efforts to identify sources of heterogeneity (eg, publication year, age, male- female ratio, follow-up interval, years of education, mean Mini-Mental State Examination score at baseline) yielded no significant results. 

Using decision-analysis modeling, Matchar et al (2001) performed a technology assessment for the Agency for Healthcare Research and Quality to examine whether  the use of FDG-PET would improve health outcomes for diagnosis of AD in 3 clinical populations: patients with dementia, patients with MCI, and subjects with no symptoms but with a first-degree relative with AD.40 For the review, a search was performed using MEDLINE, CINAHL, and the HealthSTAR databases. Eighteen articles (total N=1018 participants) were included. The reference standard used in the studies was either histopathology or clinical diagnosis. Studies reported on  various cutoffs for PET positivity, and, therefore, an unweighted summary receiver operating characteristic method was used to calculate the pooled area under the curve. Results are summarized in Table 4. Reviewers concluded that outcomes for all 3 groups were better if all patients were treated with agents such as cholinesterase inhibitors rather than limiting treatment to patients based on FDG-PET results. The rationale was that the complications of treatment were relatively  mild, and that treatment was considered to have some degree of efficacy in delaying the progression of AD.

Table 4. Results of Systematic Review on Use of FDG-PET for AD and Dementia

Study Included Studies N Outcome Estimate (95% CI)
Smailagic et al  (2015)36 14 421 Diagnostic accuracy
  • Sensitivity range: 25%-100%
  • Specificity range: 15%-100%
  • Pooled ROC (at median specificity), sensitivity: 76% (54% to 90%)
  • PLR: 4.03 (2.97 to 5.47)
  • NLR: 0.34 (0.15 to 0.75)
Davison et al  (2014)37 3 197 Diagnostic accuracy
  • Sensitivity: 84%
  • Specificity: 74%
  2 183 Diagnostic accuracy, predicting conversion from MCI to AD
  • Sensitivity range: 57%-82%
  • Specificity range: 67%-78%
  5 292 Diagnostic accuracy, differentiating AD and LBD
  • Sensitivity range: 83%-92%
  • Specificity range: 67%-93%
Bloudek et al (2011)38 20 NR Diagnostic accuracy,
  • Sensitivity: 90% (84% to 94%)
  • Specificity: 89% (81% to 94%)
  13 NR Diagnostic accuracy, AD vs other dementia
  • Sensitivity: 92% (84% to 96%)
  • Specificity: 78% (69% to 93%)
Yuan et al (2009)39 6 280 Diagnostic accuracy
  • Sensitivity: 89% (92% to 94%)
  • Specificity: 85% (78% to 90%)
  • PLR: 4.6 (3.2 to 6.7)
  • NLR: 0.15 (0.05 to 0.48)
Matchar et al (2001)40 15 729 Diagnostic accuracy
  • Sensitivity: 88% (79% to 94%)
  • Specificity: 87% (77% to 93%)
  3 289 Diagnostic accuracy, distinguishing AD from non-AD dementia
  • Sensitivity range: 86% to 95%
  • Specificity range: 61% to 74%

AD: Alzheimer's disease; CI: confidence interval; FDG-PET: fluorine 18 fluorodeoxyglucose positron emission tomography; LBD: Lewy body dementia; MCI: mild cognitive impairment; NLR: negative likelihood ratio; NR; not reported;PLR: positive likelihood ratio. 

Retrospective Studies 
In a study published after the systematic reviews, Pagani et al (2017) tested the accuracy of FDG-PET to discriminate between patients with MCI who progressed to AD and those who did not progress.41, The study population consisted of 42 normal elderly patients without MCI, 27 patients with MCI who had not converted to AD after a follow-up of at least 5 years since the first FDG-PET scan (mean follow-up, 7.5 years), and 95 patients with MCI who converted to AD within 5 years of the baseline FDG-PET (mean time to conversion, 1.8 years). The group that progressed to AD within 5 years showed significantly lower FDG-PET uptake values in the temporoparietal cortex than the other groups. Baseline FDG-PET identified patients who converted to AD with an accuracy of 89%. 

Clinically Useful 
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing. 

Direct Evidence 
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. 

Motara et al (2017) assessed the accuracy of dual-trained radiologists and nuclear medicine physicians to diagnose the type of cognitive impairment based on FDG- PET/CT images. Records of patients who had undergone FDG-PET/CT because of cognitive impairment (AD, frontotemporal dementia, mixed dementia, and dementia with Lewy bodies) following a negative CT or MRI scans were reviewed (N=136).42, Questionnaires were sent to the referring physicians to gather information on the final clinical diagnosis, usefulness of the PET/CT report, and whether the report impacted clinical management. The response rate was 72% (98/136) and mean patient follow-up was 471 days. For the diagnosis of AD, using the final clinical diagnosis as the reference standard, the sensitivity, specificity, PPV, and NPV were 87%, 97%, 93%, and 91%, respectively. Questionnaires received from the 98 physicians indicated that PET/CT: was useful (78%); had an impact on clinical management (81%); added confidence to the pretest clinical diagnosis (43%); reduced the need for further investigations (42%); changed the pretest clinical diagnosis (35%); and led to a change in therapy  (32%).

Section Summary: Suspected Alzheimer Disease 
Several systematic reviews offer evidence on FDG-PET for diagnosing AD in people with cognitive impairment and for differentiating between AD and other  dementias. Studies included in these reviews were generally poor quality. There is no standard cutoff for positive amyloid findings on PET scanning for diagnosing AD, and many studies did not include postmortem confirmation of AD as the reference standard. These limitations lead to uncertainty about estimates of performance characteristics. Although it appears that FDG-PET has high sensitivity and specificity, the evidence does not compare the performance characteristics of clinical diagnosis with PET to clinical diagnosis without PET, so the incremental value of adding PET to the standard clinical diagnosis is unclear. No studies reported on clinical outcomes of patients diagnosed with vs without FDG-PET. A single study was identified that surveyed physicians on the clinical utility of FDG-PET/CT in managing patients with cognitive impairment. In general, the physicians found the FDG-PET/CT helpful, but no clinical outcomes of patients were reported. 

Suspected Large Vessel Vasculitis Technically Reliable
Assessment of technical reliability focuses on specific tests and operators and requires review of unpublished and often proprietary information. Review of specific  tests, operators, and unpublished data are outside the scope of this evidence review and alternative sources exist. This evidence review focuses on the clinical validity and clinical utility.

Clinically Valid 
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse). 

Summaries of characteristics and results of several meta-analyses of FDG-PET that have been published on the diagnosis and management of LVV are shown in Tables 5 and 6 and are briefly described  below. 

Table 5. Characteristics of Systematic Reviews on Use of FDG-PET for Large Vessel Vasculitis

Study

Dates

Studies

N (Range)

Design

Outcomes

Lee et al (2016)43

Up to 2015

8

400 (21-93)

OBS

Diagnostic accuracy for GCA and TA

Soussan et al (2015)44

2000-2013

21

712 (18-93)

OBS

Diagnostic accuracy for GCA; assessment of disease activity in TA

Puppo et al (2014)45

1999-2014

19

977 (8-304)

OBS

Diagnostic accuracy for GCA

Treglia et al (2011)46

Up to 2011

32

604

OBS

Diagnostic accuracy for GCA and TA; assessment of disease activity; monitor treatment response

Besson et al (2011)47

Up to 2011

14

Unclear

OBS

Diagnostic accuracy for GCA

FDG-PET: fluorine 18 fluorodeoxyglucose positron emission tomography; GCA: giant cell arteritis; OBS: observational; TA: Takayasu arteritis.  

Lee et al (2016) performed a meta-analysis of the diagnostic accuracy of FDG-PET and PET/CT for LVV.43, The search included studies indexed in PubMed, EMBASE, or Cochrane Library that used the American College of Rheumatology (ACR) classification system as the reference standard diagnosis. Eight studies (total N=400 participants) were identified for inclusion. Five studies included participants with both giant cell arteritis (GCA) and Takayasu arteritis (TA) while 3 included  only GCA. Five studies evaluated FDG-PET and 3 evaluated FDG-PET/CT. Pooled estimates of sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were calculated using a random-effects model and are shown in Table 6. Interpretation of these results was limited by the use of ACR as the reference standard and the varying levels of disease activity in selected studies. 

Soussan et al (2015) conducted a literature review assessing the role of FDG-PET in the management of LVV, focused on 3 issues: determining the FDG-PET criteria for diagnosing vascular inflammation; establishing the performance of FDG-PET for the diagnosis of large vessel inflammation in GCA patients; and defining the performance of FDG-PET to evaluate the disease inflammatory activity in patients with TA.44 The MEDLINE, Cochrane Library, and EMBASE databases were searched for articles that evaluated the value of FDG-PET in LVV. Selection criteria included the use of the ACR classification for GCA or TA, the definition of a  positive amyloid threshold for PET, and more than 4 cases included. The sensitivity and specificity of FDG-PET for the diagnosis of large vessel inflammation were calculated from each selected study and then pooled for meta-analysis with a random-effects model. Disease activity was assessed with the National Institutes of Health Stroke Scale48, or another activity assessment scale. Twenty-one studies (413 patients, 299 controls) were included in the systematic review. FDG-PET showed FDG vascular uptake in 70% (288/413) of patients and 7% (22/299) of controls. Only vascular uptake equal to or greater than the liver uptake differed significantly between GCA plus TA patients and controls (p<0.001). A summary of the results is shown in Table 6. FDG-PET showed good performances in the diagnosis of large vessel inflammation, with higher accuracy for diagnosing GCA patients than for detecting activity in TA patients. Although a vascular uptake equal to or greater than the liver uptake appears to be a good criterion for diagnosing vascular inflammation, further studies would be needed to define the threshold of significance as well as the clinical significance of the vascular  uptake. 

A systematic review by Puppo et al (2014) included studies of FDG-PET in GCA comparing the diagnostic performance of qualitative and semiquantitative methods of FDG-PET interpretation.45, Reviewers selected 19 studies (442 cases, 535 controls) found in PubMed or Cochrane Library. The selected studies had various  reference standards. Ten used qualitative FDG uptake criteria to characterize inflammation, 6 used semiquantitative criteria, and 3 used both. Meta-analyses were not performed. Overall, qualitative methods were more specific but less sensitive, than semiquantitative methods. Diagnostic performance varied by vessel and by thresholds (cutoffs) for positivity. Results are shown in Table 6.  

Treglia et al (2011) published a systematic review of PET and PET/CT in patients with LVV.46, Reviewers searched MEDLINE and Scopus for publications on the role of FDG-PET in LVV. Reviewers identified 32 studies (total N=604 vasculitis patients). Selected publications related to diagnosis, assessment of disease activity, the extent of disease, response to therapy, and prediction of relapse or complications. Reviewers did not pool findings. They concluded that: (1) PET and PET/CT may   be useful for initial diagnosis and assessment of severity of disease; (2) appeared to be superior to MRI in the diagnosis of LVV, but not in assessing disease activity under immunosuppressive treatment, in predicting relapse, or in evaluating vascular complications; (3) the role of these imaging methods in monitoring treatment response is unclear. Reviewers also concluded that "given the heterogeneity between studies with regard to PET analysis and diagnostic criteria, a standardization of the technique is needed." The studies cited in support of using PET for diagnosing LVV had small sample sizes.  

Besson et al (2011) published a systematic review to assess use of FDG-PET for patients with suspected GCA; reviewers searched the MEDLINE, EMBASE, and the Cochrane databases.47 Studies were included if they evaluated the performance of FDG-PET for the diagnosis of GCA, had at least 8 participants, used ACR criteria as  the reference standard to confirm diagnosis of GCA, and included a control group. Fourteen studies were identified; the number of participants in those studies was unclear. Six studies with 283 participants (101 vasculitis, 182 controls) were included in a meta-analysis. The meta-analysis calculated pooled estimates of sensitivity, specificity, PPV, NPV, positive and negative likelihood ratio, and diagnostic accuracy using a random-effects model. Results are shown in Table 6. There was statistically significant between-study heterogeneity for sensitivity, PPV, and NPV. All studies in the meta-analysis were small case-control studies.  

Table 6. Results of Systematic Reviews Assessing Use of FDG-PET for LVV

Study

Studies

N

Outcomes

Estimate (95% CI)

Lee et al (2016)43

8

 

400

 

Diagnostic accuracy of PET and PET/CT for GCA and TA

  • Sensitivity: 76% (68% to 82%)
  • Specificity: 93% (89% to 96%)
  • PLR: 7.27 (3.71 to 14.24)
  • NLR: 0.30 (0.23 to 0.40)                                                    

 

 

 3

 

 

133 

Diagnostic accuracy of PET and PET/CT for GCA                      

  • Sensitivity: 83% (72% to 91%)
  • Specificity: 90% (80% to 96%)
  •  PLR: 7.11 (2.91 to 17.4)
  •  NLR: 0.20 (0.11 to 0.34)                                                    

Soussan et al (2015)44                                   

4     

233 

 

Diagnostic accuracy for GCA

 

  • Sensitivity: 89.5% (78.5% to 96.0%)
  • Specificity: 97.7% (CI, 94% to 99%) 
  • PLR: 28.7 (11.5 to 71.6)
  • NLR: 0.15 (0.07 to 0.29)                                                    

 

237 

Diagnostic accuracy for disease activity in TA

  • Sensitivity: 87% (78% to 93%)
  • Specificity: 73% (63% to 81%)
  • PLR: 4.2 (1.5 to 12)
  • NLR: 0.2 (0.1 to 0.5)

Puppo et al (2014)45  

10 

633 

Diagnostic accuracy for GCA

  • Sensitivity range: 56%-77%
  • Specificity range: 77%-100%
  • PPV range: 93%-100%
  • NPV range: 70%-82%

 

282 

Diagnostic accuracy for GCA

  • Sensitivity range: 58%-90%
  • Specificity range: 42%-95%
  • PPV range: 79%-89%
  • PV range: 95%-98%

 

72 

Diagnostic accuracy for GCA

  • Sensitivity range: 65%-100%
  • Specificity range: 45%-100%

Treglia et al (2011)46 

32 

604 

Diagnostic accuracy for GCA and TA; assessment of disease activity; monitor treatment response

  • No pooling; concluded that FDG-PET is useful "in the initial diagnosis and in the assessment of activity and extent of disease in patients with LVV"

Besson et al (2011)47 

283 

Diagnostic accuracy for GCA

  • Sensitivity: 80% (63% to 91%)
  • Specificity: 89% (78% to 94%)
  • PPV: 85% (62% to 95%)
  • NPV: 88% (72% to 95%)
  • PLR: 6.73 (3.55 to 12.77)
  • NLR: 0.25 (0.13 to 0.46)

CI: confidence interval; CT: computed tomography; FDG: fluorine 18 fluorodeoxyglucose; GCA: giant cell arteritis; LVV: large vessel vasculitis; NLR: negative likelihood ratio; NPV: negative predictive value; PET: positron emission tomography; PLR: positive likelihood ratio; PPV: positive predictive value; TA: Takayasu arteritis.

Clinically Useful 
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing. 

Direct Evidence 
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. 

No RCTs identified assessed the evidence on the clinical utility of FDG-PET for diagnosing LVV. 

Chain of Evidence 
Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility. 

Because the clinical validity of FDG-PET for diagnosing LVV has not been established, a chain of evidence supporting its clinical utility cannot be constructed. 

Section Summary: Suspected Large Vessel Vasculitis 
Several systematic reviews have evaluated the diagnosis and management of GCA using FDG-PET. Most studies included were small, many lacked controls, and all results were heterogeneous. Studies comparing PET with the true reference standard (biopsy or angiography) are rare. There are no consensus criteria to define the presence of vascular inflammation by FDG-PET in LVV, and different parameters with visual and semiquantitative methods have been reported. Studies demonstrating changes in management based on PET results or improvements in clinical outcomes are lacking. 

Diverse Noncardiac or Nononcologic Conditions 
Numerous systematic reviews have described the use of PET in patients with carotid stenosis49,; inflammatory diseases50,51,; fever of unknown origin52,53,54,; hyperinsulinemic hypoglycemia55,56,; spinal infections57,; mycobacterium infection58,; Creutzfeldt-Jakob disease59,; vascular prosthetic graft infection60,; prosthetic infection after knee or hip arthroplasty61,; inflammatory bowel disease62,; atypical parkinsonism63,; and Huntington disease.64, Many studies cited in these reviews  were small, retrospective, and lacked standard definitions of PET interpretation and positivity; many did not directly compare one modality with another in the same patient group or correlate the PET results in individual patients to improved clinical outcomes. 

A systematic review by Treglia et al (2011) addressed the use of FDG-PET in evaluating disease activity in patients with sarcoidosis.65, It did not include a quality assessment of individual studies. Only 3 small studies of 9 reviewed included data from a comparator imaging modality; thus, conclusions about comparative diagnostic performance cannot be  reached. 

In a systematic review of FDG-PET to diagnose prosthetic joint infection following hip or knee replacement, Kwee et al (2008) reported on a pooled sensitivity and specificity of 82.1% (95% CI, 68.0% to 90.8%) and 86.6% (95% CI, 79.7% to 91.4%), respectively.66, Reviewers noted significant heterogeneity among the 11 studies analyzed. Differences in performance were based on the location of prostheses (hip vs knee) and whether filtered back projection or iterative reconstruction was used. This meta-analysis and a study by Reinartz (2009) on the same clinical issue found that the specificity of PET was significantly greater for hip prostheses than for knee prostheses.67, Both author groups also noted that these results were based on the use of PET alone. CT is generally not useful in evaluating potential infections around  joint prostheses because of the artifacts caused by the metallic implants, so additional research would be needed on combined PET/CT. The 2009 study compared the accuracy of PET with a triple-phase scan and with WBC imaging. 

Section Summary: Diverse Noncardiac and Nononcologic Conditions 
Systematic reviews have assessed the use of FDG-PET or FDG-PET/CT for diagnosing or managing carotid stenosis, various inflammatory and immune-mediated diseases, fever of unknown origin, and various infections. However, studies included in these reviews are mostly small, retrospective, and lack standard definitions of PET interpretation and positive findings. Few studies have compared PET with other diagnostic modalities and no studies have reported on patient clinical outcomes. 

Summary of Evidence 
For individuals who have epileptic seizures who are candidates for surgery who have FDG-PET, the evidence includes systematic reviews (following the publication of 3 TEC Assessments). Relevant outcomes are symptoms, change in disease status, functional outcomes, health status measures, quality of life, hospitalizations, medication use, and resource utilization. The TEC Assessments and Program in Evidence-based Care PET recommendation report all concluded that FDG-PET accurately localizes the seizure focus compared with appropriate reference standards. A recent systematic review suggested it was difficult to discern the incremental value of FDG-PET in patients who have foci well localized by ictal scalp electroencephalography and magnetic resonance imaging. The evidence on whether FDG-PET has a predictive value for a good surgical outcome is mixed. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. 

For individuals who have suspected chronic osteomyelitis who receive FDG-PET, the evidence includes meta-analyses and a prospective study published after the meta-analyses. Relevant outcomes are test accuracy and validity, other test performance measures, change in disease status, functional outcomes, quality of life, and hospitalizations. One systematic review and meta-analysis from 2013 of 9 studies revealed that FDG-PET and FDG-PET plus computed tomography were useful for diagnosing suspected osteomyelitis in the foot of patients with diabetes. The results of another meta-analysis (2005) showed that FDG-PET was the most accurate mode (pooled sensitivity, 96%; pooled specificity, 91%) for diagnosing chronic osteomyelitis. The results appear to be robust across fairly diverse clinical populations, which strengthen the conclusions. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. 

For individuals who have suspected Alzheimer disease who receive FDG-PET, the evidence includes 5 systematic reviews of observational studies and a retrospective study assessing clinical utility. Relevant outcomes are test accuracy and validity, other test performance measures, symptoms, quality of life, and hospitalizations. The studies included in the reviews were generally of poor quality. There is no standard cutoff for PET positivity for diagnosing Alzheimer disease, and many studies have   not included postmortem confirmation of Alzheimer disease as the reference standard, leading to uncertainty about estimates of performance characteristics. FDG-PET may have high sensitivity and specificity for diagnosing Alzheimer disease, but there is little evidence comparing the performance characteristics of clinical diagnosis using PET with the clinical diagnosis not using PET; therefore, the incremental value of adding PET to the standard clinical diagnosis is unclear. No studies have    reported on clinical outcomes of patients diagnosed with and without FDG-PET. The evidence is insufficient to determine the effects of the technology on health outcomes. 

For individuals who have suspected large vessel vasculitis who receive FDG-PET, the evidence includes 5 systematic reviews of observational studies. Relevant outcomes are test accuracy and validity, other test performance measures, symptoms, morbid events, quality of life, hospitalizations, and treatment-related morbidity. Most studies included in the reviews were small and lacked controls. The reported performance characteristics were heterogeneous, but reviewers were unable to determine the source of heterogeneity. Studies comparing PET with the true reference standard of biopsy or angiography are rare. There are no consensus criteria to define the presence of vascular inflammation by FDG-PET in large vessel vasculitis, and different parameters with visual and semiquantitative methods have been reported. Studies demonstrating changes in management based on PET results or improvements in clinical outcomes are lacking. The evidence is insufficient to determine the effects of the technology on health outcomes. 

For individuals who have diverse noncardiac or nononcologic conditions (eg, central nervous system, pulmonary, and musculoskeletal diseases) who receive FDG-PET, the evidence includes a few systematic reviews. Relevant outcomes are overall survival, symptoms, change in disease status, functional outcomes, health status measures, quality of life, hospitalizations, medication use, and resource utilization. Many studies cited in the reviews were small, retrospective, and published in the 1990s to early 2000s; further, many studies did not directly compare a modality with another in the same patient group-nor did they correlate PET results in individual patients with improved clinical outcomes. Additional studies are needed to demonstrate FDG-PET results can change management, and therefore improve patient outcomes to support the utility of FDG-PET. The evidence is insufficient to determine the effect of the technology on health outcomes.

Practice Guidelines and Position Statements
American Academy of Neurology
Evidence-based practice parameters from the American Academy of Neurology are summarized in Table 7. 

Table 7. Practice Parameters on Diagnosis of Dementia

Practice Parameter

Date

PET Recommendation

Diagnosis of dementia68

2004: reaffirmed

PET imaging not recommended for routine use in diagnostic evaluation of dementia (LOR: moderate clinical certainty)

Early detection of dementia69

2003: reaffirmed

Not addressed

Diagnosis of new-onset PD70

2006: reaffirmed
2013; retired 2016

Evidence insufficient to support or refute FDG-PET as a means of distinguishing PD from other parkinsonian syndromes

Evaluation of depression, psychosis, and dementia in PD71

2006: retired 2018

Not addressed

Mild  cognitive impairment72, 

2001; 2017 

Not addressed 

FDG: fluorodeoxyglucose; LOR: level of recommendation; PD: Parkinson disease; PET: positron emission tomography.

American Academy of Orthopaedic Surgeons
The American Academy of Orthopaedic Surgeons (2010) published evidence-based, consensus guidelines.73  Fluorine 18 fluorodeoxyglucose positron emision tomography (FDG-PET) was considered:

"an option in patients in whom diagnosis of periprosthetic joint infection has not been established and are not scheduled for reoperation. (Strength of recommendation: limited (quality of the supporting evidence is unconvincing, or well-conducted studies show little clear advantage of one approach over another))" 

American College of Radiology
Evidence- and consensus-based appropriateness criteria from the American College of Radiology are summarized in Table 8.

Table 8. Appropriateness Criteria for Miscellaneous Indications of FDG-PET/CT 

Appropriateness Criteria

Last Reviewed

FDG-PET/CT Criteria

Suspected osteomyelitis, septic arthritis, or soft tissue infection (excluding spine and diabetic foot)74

2017

  • Usually not appropriate for: (1) suspected osteomyelitis with soft tissue or juxta-articular swelling with cellulitis and a skin lesion, injury, wound, ulcer, or blister; or (2) suspected osteomyelitis with pain and swelling or cellulitis associated with site of previous nonarthroplasty hardware.
  • Usually not appropriate for suspected osteomyelitis with soft-tissue or juxta-articular swelling with a history of surgery, though "this is promising new technology but data are limited."

Diagnosis of dementia75

2001, reaffirmed in 2004

 

PET imaging not recommended for routine use in diagnostic evaluation of dementia (LOR: moderate clinical certainty)

Early detection of dementia75

2001, reaffirmed in 2003, 2015

Not addressed

Diagnosis of new onset-PD75

2006: reaffirmed in 2013; retired 2016

Evidence insufficient to support or refute FDG-PET as a means of distinguishing PD from other parkinsonian syndromes

Evaluation of depression, psychosis, and dementia in PD75

2006

Not addressed

Dementia and movement disorders76

2016

May be appropriate in patients with possible or probable AD and to differentiate suspected FTD, LBD, CJD, or vascular dementia; usually not appropriate in patients with suspected HD, clinical features of PD or hemochromatosis, or motoneuron disease

Imaging after total knee arthroplasty77

2017

Usually not appropriate for routine follow-up of asymptomatic patient, in work-up for suspected periprosthetic infection, or for evaluation of prosthetic loosening

Seizures and epilepsy78

2014

Usually appropriate for surgical planning in medically refractory epilepsy; may be appropriate for new-onset seizure unrelated to trauma in adults (age ≥18 y) and for posttraumatic (subacute or chronic), new-onset seizure; otherwise, usually not appropriate for new-onset seizure

Crohn disease79

2014

Usually not appropriate

Fever without source ‒child80

2015

May be appropriate. This procedure should not be used as the initial study. Consider if extensive clinical and imaging work-up is negative.

Suspected osteomyelitis of the foot in patients with DM81

2012

Usually not appropriate

AD: Alzheimer's disease; CJD: Creutzfeldt-Jakob disease; CT: computed tomography; DM: diabetes mellitus; FDG: fluorodeoxyglucose; FTD: frontotemporal dementia; HD: Huntington disease; LBD: Lewy body disease; LOR: level of recommendation; PD: Parkinson disease; PET: positron emission tomography;

Infectious Diseases Society of America 
The Infectious Diseases Society of America (IDSA; 2015) published evidence-based, consensus guidelines on the diagnosis and treatment of native vertebral osteomyelitis in adults.82, The guidelines stated that PET "is highly sensitive for detecting chronic osteomyelitis. A negative PET scan excludes the diagnosis of osteomyelitis, including native vertebral osteomyelitis, as the sensitivity of the test is expected to be very high in view of the high concentration of red marrow in the axial skeleton." 

IDSA (2013) published evidence-based, consensus guidelines on the diagnosis and management of prosthetic joint infections.83, The guidelines concluded that PET should not be routinely used to diagnose prosthetic joint infection (strength of recommendation: B [based on moderate evidence]; quality of evidence: III [expert opinion and descriptive  studies]). 

IDSA (2012) published evidence-based, consensus guidelines on the diagnosis and treatment of diabetic foot infections.84, The guidelines concluded that the role of FDG-PET in evaluating a diabetic foot infection has not been established. 

IDSA (2018) will be publishing guidelines on the diagnosis and management of bone and joint infections in children. 

U.S. Preventive Services Task Force Recommendations 
Not applicable.

ONGOING AND UNPUBLISHED CLINICAL TRIALS
Currently, unpublished trials that might influence this review are listed in Table 9. 

Table 9. Summary of Key Trials

NCT No. Trial Name Planned Enrollment Completion Date
Ongoing

NCT00811122

Biodistribution of 11C-PIB PET in Alzheimer’s Disease, Frontotemporal Dementia, and Cognitively Normal Elderly  

30  Apr 2018 (ongoing) 

NCT03022968

Tau Brain Imaging in Typical and Atypical Alzheimer’s Disease  

24  Sep 2018 

NCT02084147 

PET-MRI: Evaluation, Optimization and Clinical Implementation 

530  Oct 2018

NCT00194298

FDG-PET Imaging in Complicated Diabetic Foot  

240  Jan 2020 

NCT02771483

Improving the Diagnosis and Prognostication of Giant Cell Arteritis through the Novel Use of Positron Emission Tomography (PET), Microbiological and Immune Biomarkers  

50  Feb 2020 

Unpublished

NCT00329706

Early and Long-Term Value of Imaging Brain Metabolism

710 Jan 2017 (completed)

NCT: national clinical trial.

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  84. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. Jun 2012;54(12):e132-173. PMID   22619242
  85. Centers for Medicare & Medicaid Services (CMS). Decision Memo for Positron Emission Tomography (FDG) and Other Neuroimaging Devices for Suspected Dementia  (CAG-00088R).  2004;   https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx? NCAId=104&NcaName=Positron+Emission+Tomography+(FDG)+and+Other+Neuroimaging+Devices+for+Suspected+Dementia+ (1st+Recon)&bc=AiAAAAAAEAAA&. Accessed August 24,   2018.
  86. Centers for Medicare & Medicaid Services (CMS). National Coverage Determination (NCD) for FDG PET for Dementia and Neurodegenerative Diseases (220.6.13).   2009;  https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx? NCDId=288&ncdver=3&DocID=220.6.13&SearchType=Advanced&bc=IAAAABAAAAAAAA%3d%3d&.  Accessed  August  24,  2018.
  87. Centers for Medicare & Medicaid Services (CMS). National Coverage Determination for FDG PET for Infection and Inflammation (220.6.16). 2008; https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx? NCDId=323&ncdver=1&CoverageSelection=National&KeyWord=pet&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAABAAAAAAAA%3d%3d&. Accessed August 24, 2018..

Coding Section

Codes Number Description
CPT 78608

Brain imaging, PET, metabolic evaluation

  78609 Brain imaging, PET, perfusion evaluation
  78811-78813 Positron emission tomography (PET) imaging code range
  78814-78816 Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging code range
ICD-9 Procedure 92.01-92.19 Radioisotope scanning code range (includes PET scans)
ICD-9 Diagnosis 345.00-345.91 Epilepsy, code range
  730.10-730.19 Chronic osteomyelitis code range
HCPCS A9526 Nitrogen N-13 ammonia, diagnostic, per study dose, up to 40 millicuries
  A9552 Fluorodeoxyglucose F-18 FDG, diagnostic, per study dose, up to 45 millicuries
  A9580 Sodium fluoride F-18, diagnostic, per study dose, up to 30 millicuries
ICD-10-CM (effective 10/01/15) G40.001-G40.919 Epilepsy and recurrent seizures code range
  M86.30-M86.69 Chronic osteomyelitis code range
ICD-10-PCS (effective 10/01/15) C030BZZ, C030KZZ, C030MZZ, C030YZZ Nuclear medicine, central nervous system, positron emission tomography (PET), brain, code by radionuclide
    There are no specific codes for PET of the musculoskeletal system. The following codes might be used.
 

CP211ZZ,CP21YZZ,CP221ZZ,
CP22YZZ,CP231ZZ,CP23YZZ,
CP241ZZ,CP24YZZ,CP261ZZ,
CP26YZZ,CP271ZZ,CP27YZZ,
CP281ZZ,CP28YZZ,CP291ZZ,
CP29YZZ,CP2B1ZZ, CP2BYZZ,
CP2C1ZZ, CP2CYZZ,CP2D1ZZ,
CP2DYZZ,CP2F1ZZ, CP2FYZZ,
CP2G1ZZ,CP2GYZZ, CP2H1ZZ,
CP2HYZZ,CP2J1ZZ, CP2JYZZ,
CP2YYZZ

Nuclear medicine, musculoskeletal system, tomographic nuclear medicine imaging, codes by body part and radionuclide used
Type of Service Radiology  
Place of Service Inpatient/Outpatient/Physician's Office  

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

02/13/2019 

Annual review, adding fever of unknown origin and inflammation of unknown origin to investigational list. No other changes to policy intent. Also updating rationale and references. 

03/08/2018 

Annual review, no change to policy intent. Updating title to maintain consistency with industry terminology. Also updating regulatory status, rationale and references. 

02/03/2017 

Annual review, no change to policy intent. Adding Fluorodeoxygucose F18 to the title and FDG to the investigational status. Also updating background, description, regulatory status, rationale and references. 

02/02/2016 

Annual review, no change to policy intent. Updating background, description, rationale and references.

03/03/2015 

Annual review, no change to policy intent. Updated guidelines, rationale and references. Added related policies and coding. 

02/24/2014

Annual review. Updated background, description, rationale and references.  No change to policy intent.


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