Cellular and Molecular Diversity in Scleroderma.

With the increasing armamentarium of high-throughput tools available at manageable cost, it is attractive and informative to determine the molecular underpinnings of patient heterogeneity in systemic sclerosis (SSc). Given the highly variable clinical outcomes of patients labelled with the same diagnosis, unravelling the cellular and molecular basis of disease heterogeneity will be crucial to predicting disease risk, stratifying management and ultimately informing a patient-centered precision medicine approach. Herein, we summarise the findings of the past several years in the fields of genomics, transcriptomics, and proteomics that contribute to unraveling the cellular and molecular heterogeneity of SSc. Expansion of these findings and their routine integration with quantitative analysis of histopathology and imaging studies into clinical care promise to inform a scientifically driven patient-centred personalized medicine approach to SSc in the near future.

Novel transcatheter closure of an iatrogenic perimembranous ventricular septal defect.

Iatrogenic membranous ventricular septal defects (VSD) are rare complications of cardiothoracic surgery, most commonly seen as a complication of aortic valve replacements. An iatrogenic VSD can lead to right sided heart failure, systemic hypoxia, and arrhythmias, and closure is often necessary. Given the increased mortality associated with repeat surgical procedures, percutaneous transcatheter closure of these iatrogenic VSDs has increasingly become the preferred choice of therapy. We describe the first case of iatrogenic membranous VSD in the setting of mitral valve replacement and tricuspid valve repair, using the newly approved Amplatzer Duct Occluder II Device from an entirely retrograde approach. © 2014 Wiley Periodicals, Inc.

Right ventricular strain in pulmonary arterial hypertension: a 2D echocardiography and cardiac magnetic resonance study.

BACKGROUND: Right ventricular (RV) strain is a potentially useful prognostic marker in patients with pulmonary arterial hypertension (PAH). However, published reports regarding the accuracy of two-dimensional echocardiography (2DE)-derived RV strain against an independent reference in this patient population are limited. The aims of this study were: (1) to study the relationship between 2DE RV longitudinal strain and cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (RVEF) in patients with PAH; (2) to compare 2DE-derived and CMR-derived RV longitudinal strain in these patients; and (3) to determine the reproducibility of these measurements. METHODS: Thirty patients with PAH underwent 2DE and CMR imaging within a 2-hour time period. 2DE RV longitudinal strain was measured from a focused RV apical four-chamber view using speckle tracking software. CMR RV longitudinal strain was measured from short-axis slices acquired using fast-strain-encoded sequence. Global peak systolic RV longitudinal strain was calculated for both 2DE and CMR. RESULTS: RV longitudinal strain using 2DE software correlated well with CMR-derived RVEF (R = 0.69, P = 0.0006). There was moderate agreement when comparing 2DE to CMR RV longitudinal strain (R = 0.74, P = 0.0002; bias -1%, limits of agreement -9 to 7%). Inter-observer variability and intra-observer variability for RV longitudinal strain were lower for 2DE than CMR. CONCLUSIONS: RV longitudinal strain by 2DE provides a good alternative for CMR-derived RVEF in patients with PAH. The moderate agreement in strain measurements between 2DE and CMR suggests that further software improvements are needed before these measurements can be used interchangeably in clinical practice.

Classification of CT pulmonary angiography reports by presence, chronicity, and location of pulmonary embolism with natural language processing.

In this paper we describe an efficient tool based on natural language processing for classifying the detail state of pulmonary embolism (PE) recorded in CT pulmonary angiography reports. The classification tasks include: PE present vs. absent, acute PE vs. others, central PE vs. others, and subsegmental PE vs. others. Statistical learning algorithms were trained with features extracted using the NLP tool and gold standard labels obtained via chart review from two radiologists. The areas under the receiver operating characteristic curves (AUC) for the four tasks were 0.998, 0.945, 0.987, and 0.986, respectively. We compared our classifiers with bag-of-words Naive Bayes classifiers, a standard text mining technology, which gave AUC 0.942, 0.765, 0.766, and 0.712, respectively.

ACR Appropriateness Criteria ® imaging of mesenteric ischemia.

Mesenteric ischemia is a rare disease associated with high morbidity and mortality. Acute mesenteric ischemia is most commonly secondary to embolism followed by arterial thrombosis, nonocclusive ischemia, and less commonly venous thrombosis. Chronic mesenteric ischemia is almost always caused by atherosclerotic disease, with rare causes including fibromuscular dysplasia and vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Patients with mesenteric ischemia usually present with nonspecific abdominal symptoms and laboratory findings. This document evaluates and rates the appropriateness of imaging to evaluate patients with clinically suspected mesenteric ischemia. While catheter-based angiography has been considered the reference standard and enables diagnosis and treatment, advances in computed tomography have made it a first-line test in many patients because it is a fast, widely available, and noninvasive study. Abdominal radiographs and ultrasound have a limited role in diagnosing mesenteric ischemia but are commonly the first ordered tests in patients with abdominal pain and may diagnose more common pathologies.

ACR Appropriateness Criteria® Workup of Noncerebral Systemic Arterial Embolic Source.

Noncerebral systemic arterial embolism, which can originate from cardiac and noncardiac sources, is an important cause of patient morbidity and mortality. When an embolic source dislodges, the resulting embolus can occlude a variety of peripheral and visceral arteries causing ischemia. Characteristic locations for noncerebral arterial occlusion include the upper extremities, abdominal viscera, and lower extremities. Ischemia in these regions can progress to tissue infarction resulting in limb amputation, bowel resection, or nephrectomy. Determining the source of arterial embolism is essential in order to direct treatment decisions. This document reviews the appropriateness category of various imaging procedures available to determine the source of the arterial embolism. The variants included in this document are known arterial occlusion in the upper extremity, lower extremity, mesentery, kidneys, and multiorgan distribution that are suspected to be of embolic etiology. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Dialysis Fistula Malfunction.

The creation and maintenance of a dialysis access is vital for the reduction of morbidity, mortality, and cost of treatment for end stage renal disease patients. One's longevity on dialysis is directly dependent upon the quality of dialysis. This quality hinges on the integrity and reliability of the access to the patient's vascular system. All methods of dialysis access will eventually result in dialysis dysfunction and failure. Arteriovenous access dysfunction includes 3 distinct classes of events, namely thrombotic flow-related complications or dysfunction, nonthrombotic flow-related complications or dysfunction, and infectious complications. The restoration of any form of arteriovenous access dysfunction may be supported by diagnostic imaging, clinical consultation, percutaneous interventional procedures, surgical management, or a combination of these methods. This document provides a rigorous evaluation of how variants of each form of dysfunction may be appraised and approached systematically. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Lower Extremity Chronic Venous Disease.

Lower extremity venous insufficiency is a chronic medical condition resulting from primary valvular incompetence or, less commonly, prior deep venous thrombosis or extrinsic venous obstruction. Lower extremity chronic venous disease has a high prevalence with a related socioeconomic burden. In the United States, over 11 million males and 22 million females 40 to 80 years of age have varicose veins, with over 2 million adults having advanced chronic venous disease. The high cost to the health care system is related to the recurrent nature of venous ulcerative disease, with total treatment costs estimated >$2.5 billion per year in the United States, with at least 20,556 individuals with newly diagnosed venous ulcers yearly. Various diagnostic and treatment strategies are in place for lower extremity chronic venous disease and are discussed in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial.

BACKGROUND: Non-randomised studies of haemopoietic stem-cell transplantation (HSCT) in systemic sclerosis have shown improvements in lung function and skin flexibility but high treatment-related mortality. We aimed to assess safety and efficacy of autologous non-myeloablative HSCT in a phase 2 trial compared with the standard of care, cyclophosphamide. METHODS: In our open-label, randomised, controlled phase 2 trial, we consecutively enrolled patients at Northwestern Memorial Hospital (Chicago, IL, USA) who were aged younger than 60 years with diffuse systemic sclerosis, modified Rodnan skin scores (mRSS) of more than 14, and internal organ involvement or restricted skin involvement (mRSS <14) but coexistent pulmonary involvement. We randomly allocated patients 1:1 by use of a computer-generated sequence with a mixed block design (blocks of ten and four) to receive HSCT, 200 mg/kg intravenous cyclophosphamide, and 6·5 mg/kg intravenous rabbit antithymocyte globulin or to receive 1·0 g/m(2) intravenous cyclophosphamide once per month for 6 months. The primary outcome for all enrolled patients was improvement at 12 months' follow-up, defined as a decrease in mRSS (>25% for those with initial mRSS >14) or an increase in forced vital capacity by more than 10%. Patients in the control group with disease progression (>25% increase in mRSS or decrease of >10% in forced vital capacity) despite treatment with cyclophosphamide could switch to HSCT 12 months after enrolment. This study is registered with ClinicalTrials.gov, number NCT00278525. FINDINGS: Between Jan 18, 2006, and Nov 10, 2009 we enrolled 19 patients. All ten patients randomly allocated to receive HSCT improved at or before 12 months' follow-up, compared with none of nine allocated to cyclophosphamide (odds ratio 110, 95% CI 14·04-∞; p=0·00001). Eight of nine controls had disease progression (without interval improvement) compared with no patients treated by HSCT (p=0·0001), and seven patients switched to HSCT. Compared with baseline, data for 11 patients with follow-up to 2 years after HSCT suggested that improvements in mRSS (p<0·0001) and forced vital capacity (p<0·03) persisted. INTERPRETATION: Non-myeloablative autologous HSCT improves skin and pulmonary function in patients with systemic sclerosis for up to 2 years and is preferable to the current standard of care, but longer follow-up is needed. FUNDING: None.

Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson.

BACKGROUND: Adenosine cardiovascular magnetic resonance (CMR) can accurately quantify myocardial perfusion reserve. While regadenoson is increasingly employed due to ease of use, imaging protocols have not been standardized. We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) - more specifically, whether regadenoson stress imaging should be performed before or after rest imaging. METHODS: Twenty healthy subjects underwent CMR perfusion imaging during resting conditions, during regadenoson-induced hyperemia (0.4 mg), and after 15 min of recovery. In 10/20 subjects, recovery was facilitated with aminophylline (125 mg). Myocardial time-intensity curves were used to obtain left ventricular cavity-normalized myocardial up-slopes. MPRi was calculated in two different ways: as the up-slope ratio of stress to rest (MPRi-rest), and the up-slope ratio of stress to recovery (MPRi-recov). RESULTS: In all 20 subjects, MPRi-rest was 1.78 ± 0.60. Recovery up-slope did not return to resting levels, regardless of aminophylline use. Among patients not receiving aminophylline, MPRi-recov was 36 ± 16% lower than MPRi-rest (1.13 ± 0.38 vs. 1.82 ± 0.73, P = 0.001). In the 10 patients whose recovery was facilitated with aminophylline, MPRi-recov was 20 ± 24% lower than MPRi-rest (1.40 ± 0.35 vs. 1.73 ± 0.43, P = 0.04), indicating incomplete reversal. In 3 subjects not receiving aminophylline and 4 subjects receiving aminophylline, up-slope at recovery was greater than at stress, suggesting delayed maximal hyperemia. CONCLUSIONS: MPRi measurements from regadenoson CMR are underestimated if recovery perfusion is used as a substitute for resting perfusion, even when recovery is facilitated with aminophylline. True resting images should be used to allow accurate MPRi quantification. The delayed maximal hyperemia observed in some subjects deserves further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00871260.

ACR Appropriateness Criteria(®) blunt chest trauma--suspected aortic injury.

The purpose of these guidelines is to recommend appropriate imaging for patients with blunt chest trauma. These patients are most often imaged in the emergency room, and thus emergency radiologists play a substantial role in prompt, accurate diagnoses that, in turn, can lead to life-saving interventions. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Imaging largely focuses on the detection and exclusion of traumatic aortic injury; a large proportion of patients are victims of motor vehicle accidents. For those patients who survive the injury and come to emergency radiology, rapid, appropriate assessment of patients who require surgery is paramount.

ACR Appropriateness Criteria® Nontraumatic Aortic Disease.

Nontraumatic aortic disease can be caused by a wide variety of disorders including congenital, inflammatory, infectious, metabolic, neoplastic, and degenerative processes. Imaging examinations such as radiography, ultrasound, echocardiography, catheter-based angiography, CT, MRI, and nuclear medicine examinations are essential for diagnosis, treatment planning, and assessment of therapeutic response. Depending upon the clinical scenario, each of these modalities has strengths and weaknesses. Whenever possible, the selection of a diagnostic imaging examination should be based upon the best available evidence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. The purpose of this document is to assist physicians select the most appropriate diagnostic imaging examination for nontraumatic aortic diseases.

ACR Appropriateness Criteria® Radiologic Management of Portal Hypertension.

Cirrhosis is a heterogeneous disease that cannot be studied as a single entity and is classified in two main prognostic stages: compensated and decompensated cirrhosis. Portal hypertension, characterized by a pathological increase of the portal pressure and by the formation of portal-systemic collaterals that bypass the liver, is the initial and main consequence of cirrhosis and is responsible for the majority of its complications. A myriad of treatment options exists for appropriately managing the most common complications of portal hypertension, including acute variceal bleeding and refractory ascites. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Noncerebral Vasculitis.

Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Retroperitoneal Bleed.

The initial diagnosis of retroperitoneal bleeding can be challenging by physical examination and clinical presentation. Prompt imaging can make the diagnosis and be lifesaving. When selecting appropriate imaging for these patient's, consideration must be made for sensitivity and ability to image the retroperitoneum, as well as speed of imaging.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Upper Extremity Deep Vein Thrombosis.

This publication includes the appropriate imaging modalities to assess suspected deep vein thrombosis in the upper extremities. Ultrasound duplex Doppler is the most appropriate imaging modality to assess upper-extremity deep vein thrombosis. It is a noninvasive test, which can be performed at the bedside and used for serial evaluations. Ultrasound can also directly identify thrombus by visualizing echogenic material in the vein and by lack of compression of the vein walls from manual external pressure. It can indirectly identify thrombus from altered blood-flow patterns. It is most appropriate in the evaluation of veins peripheral to the brachiocephalic vein. CT venography and MR venography are not first-line imaging tests, but are appropriate to assess the central venous structures, or to assess the full range of venous structures from the hand to the right atrium. Catheter venography is appropriate if therapy is required. Radionuclide venography and chest radiography are usually not appropriate to assess upper-extremity deep vein thrombosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Thoracic Outlet Syndrome.

Thoracic outlet syndrome (TOS) is the clinical entity that occurs with compression of the brachial plexus, subclavian artery, and/or subclavian vein at the superior thoracic outlet. Compression of each of these structures results in characteristic symptoms divided into three variants: neurogenic TOS, venous TOS, and arterial TOS, each arising from the specific structure that is compressed. The constellation of symptoms in each patient may vary, and patients may have more than one symptom simultaneously. Understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes is important in choosing and interpreting radiological imaging performed to help diagnose TOS and plan for intervention. This publication has separated imaging appropriateness based on neurogenic, venous, or arterial symptoms, acknowledging that some patients may present with combined symptoms that may require more than one study to fully resolve. Additionally, in the postoperative setting, new symptoms may arise altering the need for specific imaging as compared to preoperative evaluation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Clinically Suspected Vascular Malformation of the Extremities.

Vascular malformations of the extremities represent a wide spectrum of lesions, broadly divided into high-flow and low-flow categories. High-flow lesions include arteriovenous malformations and arteriovenous fistulas, while the more common low-flow lesions consist of venous and lymphatic malformations. The clinical presentation of vascular malformations is variable and can include extremity pain, discoloration, focal mass, or diffuse extremity enlargement. A vascular murmur can also be present and is more typical of high-flow lesions. While vascular malformations can often be diagnosed or strongly suspected by clinical features alone, imaging is often used to confirm the diagnosis, determine lesion characteristics and extent, and/or plan for treatment. Among the imaging options available, those usually appropriate for initial imaging of suspected vascular malformation are MR angiography without and with intravenous contrast, MRI without and with intravenous contrast, CT angiography with intravenous contrast, or US duplex Doppler. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Nonatherosclerotic Peripheral Arterial Disease.

A broad range of nonatherosclerotic diseases affect the peripheral arteries. The appropriate initial diagnostic imaging studies vary, depending upon the clinical presentation and suspicion of disease. Accurate vascular imaging relies upon visualization of the vessel lumen, vessel wall, and surrounding soft-tissue structures, with some modalities also offering the ability to characterize blood flow direction and velocity. Furthermore, nonvascular findings are often paramount in supporting a suspected clinical syndrome or guiding surgical management. The scenarios discussed in this document include the initial evaluation of suspected popliteal entrapment syndrome, external iliac artery endofibrosis, lower-extremity inflammatory vasculitides, dissection or connective tissue disease, noninflammatory vascular disease, and vascular trauma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.