Stimulation of the vagus nerve can be performed using a pulsed electrical stimulator implanted within the carotid artery sheath. This technique has been proposed as a treatment for refractory seizures, depression, and other disorders. There are also devices available that are implanted at different areas of the vagus nerve. This evidence review also addresses devices that stimulate the vagus nerve transcutaneously.

Spinal cord stimulation delivers low-voltage electrical stimulation to the dorsal columns of the spinal cord to block the sensation of pain; this is achieved through a surgically implanted spinal cord stimulation device, which comes equipped with a radiofrequency receiver. The neurostimulator device is also issued with a standard power source (battery) that can be implanted or worn externally. Other neurostimulators target the dorsal root ganglion.

Bulking agents are injectable substances used to increase tissue bulk. They can be injected periurethrally to treat urinary incontinence and perianally to treat fecal incontinence. The U.S. Food and Drug Administration (FDA) has approved several bulking agent products for treating urinary incontinence and one for treating fecal incontinence.

Transurethral destruction of prostate tissue by microwave therapy is an alternative to transurethral resection of the prostate (TURP) for patients suffering from benign prostatic hyperplasia. The purpose of microwave thermotherapy is the destruction of the prostatic adenoma in the lateral lobes of the prostate, to improve the symptoms and the elimination of urine. This technology involves placing a catheter containing a microwave antenna at the level of the prostate and limiting microwave radiation at this level. Water is circulated in the catheter to cool the urethra. A Foley-type balloon is inflated at the end of the catheter to control the position of the catheter. Fiberoptic sensors monitor the temperature of the rectum and urethra. Electromagnetic waves emit high-energy photons that interact with prostate tissue, producing heat. Microwave thermotherapy produces coagulation necrosis in the lateral lobes of the prostate up to a distance of 17mm from the urethra, preserving the urethral surface, distal sphincter, urethral mucosa, bladder neck, and prostatic periphery. <a id="

Bronchial thermoplasty is a potential treatment option for individuals with severe persistent asthma. It consists of radiofrequency energy delivered to the distal airways with the aim of decreasing smooth muscle mass believed to be associated with airway inflammation.

Sacral nerve neuromodulation, also known as sacral nerve stimulation, involves the implantation of a permanent device that modulates the neural pathways controlling bladder or rectal function. This evidence review addresses the use of sacral nerve neuromodulation to treat urinary or fecal incontinence, fecal nonobstructive retention, and chronic pelvic pain in patients with intact neural innervation of the bladder and/or rectum.

Transurethral radiofrequency needle ablation of the prostate (also known as TUNA or RFNA) of the prostate has been proposed as an alternative to transurethral resection of the prostate (TURP) for treatment of benign prostatic hyperplasia (BPH). Other alternatives include transurethral incision of the prostate, intraurethral stents, balloon dilation, heat therapy (e.g., microwave hyperthermia), high-intensity focused ultrasound (HIFU), roller ball transurethral vaporization of the prostate, and laser prostatectomy. The mechanism of TUNA is thermal coagulation necrosis. The TUNA procedure is performed under direct vision. The intraurethral components are contained in a sheath, including 2 flexible needles that are deployed into the lateral lobes of the prostate adenoma to a depth determined by transrectal ultrasound measurement. Each lobe is treated 2 to 4 times, and the procedure averages 30 minutes in length. <a id="

Complete Guidelines available at https://www.aace.com/publications/guidelines. Endocr Pract. Jul 2016; 22(7): 842-84. PMID 27472012″>1,

Obstructive sleep apnea (OSA) syndrome is characterized by repetitive episodes of upper airway obstruction due to the collapse of the upper airway during sleep. For individuals who have failed conservative therapy, established surgical approaches may be indicated. This evidence review addresses minimally invasive surgical procedures for the treatment of OSA. They include laser-assisted uvuloplasty, tongue base suspension, radiofrequency volumetric reduction of palatal tissues and base of tongue, palatal stiffening procedures, and hypoglossal nerve stimulation (HNS). This evidence review does not address conventional surgical procedures such as uvulopalatopharyngoplasty (UPPP), hyoid suspension, surgical modification of the tongue, maxillofacial surgery, or adenotonsillectomy.

Endovascular stent grafts can be used as minimally invasive alternatives to open surgical repair for treatment of abdominal aortic aneurysms (AAAs). Open surgical repair of AAAs has high morbidity and mortality, and endovascular grafts have the potential to reduce the operative risk associated with AAA repair.

In the appendicular skeleton, electrical stimulation with either implantable electrodes or noninvasive surface stimulators has been investigated to facilitate the healing of fresh fractures, stress fractures, delayed union, nonunion, congenital pseudarthrosis, and arthrodesis.

The Ilizarov bone-lengthening procedure uses a circular external fixator device that attaches to the bone via transfixion wires. A corticotomy (percutaneous osteotomy) is performed, permitting attachment of the wires. Periodic adjustment of the external fixator produces a distractive lengthening force, which gradually stimulates new bone growth. <a id="

Minimally Invasive Breast Biopsy (MIBB) is a breast biopsy that is done with a needle to obtain a diagnosis of a breast abnormality. There are three different types of MIBB. Breast biopsy methods include core needle biopsy (CNB), fine needle aspiration (FNA), surgical biopsy, and skin punch biopsy. Based on the prebiopsy imaging, the radiologist makes an assessment of which approach will yield the highest likelihood of success, while considering patient safety and comfort. The imaging findings are correlated with the clinical exam to determine whether the chosen biopsy target(s) account for the clinical abnormality. The requirements of subsequent therapy and/or clinical trial (eg, marker clip placement, tissue banking) are additional factors that are included in biopsy planning. The choice of imaging guidance depends upon the modality on which the lesion is best visualized and whether it is palpable. Patient factors such as tolerance for positioning (eg, prone position is usually needed for stereotactic or magnetic resonance imaging [MRI] guidance) are also considered. <a id="

Reconstructive breast surgery is defined as a surgical procedure that is designed to restore the normal appearance of the breast after surgery, accidental injury, or trauma. Breast reconstruction is distinguished from purely cosmetic procedures by the presence of a medical condition, e.g., breast cancer or trauma, which leads to the need for breast reconstruction.

Macromastia, or gigantomastia, is a condition that describes breast hyperplasia or hypertrophy. Macromastia may result in clinical symptoms such as shoulder, neck, or back pain, or recurrent intertrigo in the mammary folds. In addition, macromastia may be associated with psychosocial or emotional disturbances related to the large breast size. Reduction mammaplasty is a surgical procedure designed to remove a variable proportion of breast tissue to address emotional and psychosocial issues and/or to relieve the associated clinical symptoms.

A variety of treatment modalities are available to treat varicose veins/venous insufficiency, including surgery, thermal ablation, sclerotherapy, mechanochemical ablation (MOCA), cyanoacrylate adhesive (CAC), and cryotherapy. The application of each modality is influenced by the severity of the symptoms, type of vein, source of venous reflux, and the use of other (prior or concurrent) treatment.

Cryoablation, also known as cryotherapy or cryosurgery, is a procedure that attacks cancer cells using extremely cold gas. This technique can be used to treat prostate cancer by percutaneously inserting thin, needle-like cryoprobes into the prostate gland and then sending very cold gas down the cryoprobes to rapidly freeze and thaw the tissue, causing necrosis. This review evaluates evidence on the use of total (whole gland, definitive therapy) cryoablation. Subtotal (focal) cryoablation and alternative procedures are considered in evidence review 8.01.61.

Transurethral water vapor thermal therapy and transurethral waterjet ablation (aquablation) have been investigated as minimally invasive alternatives to transurethral resection of the prostate (TURP), considered the traditional standard treatment for benign prostatic hyperplasia (BPH). Transurethral water vapor thermal therapy uses radiofrequency-generated water vapor (~103°C) thermal energy based on the thermodynamic properties of convective versus conductive heat transfer to ablate prostate tissue. Aquablation cuts tissue by using a pressurized jet of fluid delivered to the prostatic urethra.

Computer-assisted navigation in orthopedic procedures describes the use of computer-enabled tracking systems to facilitate alignment in a variety of surgical procedures, including fixation of fractures, ligament reconstruction, osteotomy, tumor resection, preparation of the bone for joint arthroplasty, and verification of the intended implant placement.

Thoracic endovascular aortic repair (TEVAR) involves the percutaneous placement of a stent graft in the descending thoracic or thoracoabdominal aorta. It is a less invasive alternative than open surgery for the treatment of thoracic aortic aneurysms (TAAs), dissections, or rupture, and thus has the potential to reduce the morbidity and mortality of open surgery. Endovascular stenting may also be an alternative to medical therapy for treating TAAs or thoracic aorta dissections.

Gastric electrical stimulation (GES) is performed using an implantable device designed to treat chronic drug-refractory nausea and vomiting secondary to gastroparesis of diabetic, idiopathic, or postsurgical etiology. GES has also been investigated as a treatment of obesity. The device may be referred to as a gastric pacemaker.

Cryosurgical ablation (hereafter referred to as cryosurgery or cryoablation) involves freezing of target tissues; this is most often performed by inserting a coolant-carrying probe into the tumor. Cryosurgery may be performed as an open surgical technique or as a closed procedure under laparoscopic or ultrasound guidance.

Laser energy (laser discectomy) and radiofrequency coblation (nucleoplasty) are being evaluated for decompression of the intervertebral disc. For laser discectomy under fluoroscopic guidance, a needle or catheter is inserted into the disc nucleus, and a laser beam is directed through it to vaporize tissue. For disc nucleoplasty, bipolar radiofrequency energy is directed into the disc to ablate tissue. These minimally invasive procedures are being evaluated for the treatment of discogenic back pain.

Percutaneous balloon valvuloplasty is a method of treating stenotic pulmonary, mitral, and aortic valves without open surgery. For pulmonary valvuloplasty, a balloon-tipped catheter is passed from the femoral or brachial vein into the right atrium. From there it is threaded just to the entrance of the right ventricle, the site of the pulmonic valve. By puncturing the atrial septum, access can also be obtained for either the mitral or aortic valves. The femoral artery can also be used to avoid septal puncture. When the balloon is positioned at the heart valve, a series of inflation-deflation cycles are required to relieve stenosis <a id="

Breast duct endoscopy is a technique that provides for direct visual examination of the breast ducts through nipple orifice cannulation and exploration. The technique has been investigated in the following clinical situations:

Diagnostic technique in women with spontaneous nipple discharge, where endoscopy might function as an alternative to surgical excision
Technique to obtain cellular material to stratify women for risk of breast cancer
As a follow-up test for women with atypical cytology as detected by ductal lavage (see policy No. 2.01.45)
Delineation of intraductal disease to define margins of surgical resection
The direct delivery of therapeutic agents, including photodynamic therapy, laser ablation, topical biological agents, etc.
Of related interest, three-dimensional reconstruction techniques of computed tomography scans are now being studied in another approach referred to as virtual ductoscopy.

Implantable infusion pumps can provide long-term drug infusion at constant or variable rates; several devices are commercially available. Pain For individuals who have cancer pain who receive intravenous, intrathecal, or epidural injection of opioids with an implantable infusion pump, the evidence includes randomized controlled trials and a systematic review. Relevant outcomes are symptoms, quality of life, and treatment-related morbidity. A systematic review identified 2 randomized controlled trials on implantable infusion pumps for cancer pain; one did not find a difference between groups in pain scores but was likely underpowered. The other found a higher rate of pain reduction with an implantable pump compared with medical management alone; the difference between groups was marginally significant. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals who have severe, chronic, intractable noncancer pain who receive intravenous, intrathecal, or epidural injection of opioids with an implantable infusion pump, the evidence includes observational studies and systematic reviews. Relevant outcomes are symptoms, quality of life, and treatment-related morbidity. A 2013 systematic review of retrospective and prospective cohort studies indicated reduced pain with intrathecal opioids. A 2009 systematic review included 4 observational studies; 2 showed positive results for pain relief, 1 study had negative results, and results for the fourth were unavailable. The evidence is insufficient to determine the effects of the technology on health outcomes. Severe Spasticity For individuals who have severe spasticity of cerebral or spinal cord origin, unresponsive to or intolerant of oral therapy, who receive intrathecal baclofen with an implantable infusion pump, the evidence includes observational studies, a nonrandomized comparative study, and systematic reviews. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Uncontrolled studies and systematic reviews of these studies have reported improvements in spasticity for patients treated using implantable infusion pumps. A nonrandomized comparative study comparing patients using implantable infusion pumps for baclofen delivery with patients on a wait list found significantly greater reductions in spasticity in the group with pump implantation on some outcomes, but not others. Randomized controlled trials are lacking. The evidence is insufficient to determine the effects of the technology on health outcomes. Because of the strong rationale for use, suggestive evidence, and support from clinical guidelines, infusion pumps may be considered medically necessary for cancer pain, chronic, intractable noncancer pain, and severe spasticity. <a id="

Since early in the 1970s, there was evidence that supported the theory that firm control of diabetes prevented or slowed the complications of Type I diabetes. This was helped by the development of reliable methods of assessing glycemic control (Hb A1c) and the development of accurate methods of assessing diabetes. The "Diabetic Control and Complication Trial" (DCCT) proved that tight control of diabetes prevented or slowed the chronic complications of this condition. In the study arm in which patients received intensive treatment, either by multiple daily injections (MDI) or by continuous subcutaneous insulin infusion (CSII) there was a 70% reduction in the progression of diabetic retinopathy; 50% reduction in diabetic nephropathy and 64% reduction in diabetic neuropathy. Based on these results the "American Diabetes Association" revised its standard of care and recommended target glycemic control at normal levels in most patients with Type I Diabetes. The continuous infusion system ("Continuous Subcutaneous Insulin Infusion- CSSI") is a system of subcutaneous insulin infusion using a programmable pump that provides a continuous and stable flow. This flow can be programmed to manage the amount depending on the metabolic needs of the patient who is using it. It can be programmed to supply greater amounts of insulin to cover meals intake. This provides the patient more flexibility to suit their lifestyles. Some studies show that users of this system maintain levels of glycosylated hemoglobin (Hb A1c) within normal ranges, hypoglycemic episodes are reduced, and fewer emergency room visits and hospitalizations. This system has the following advantages: Improves metabolic control and glucose levels are achieved near normal • Reduce the risk of micro and macrovascular complications: 1. retinopathies reduce the risk of developing it by 76%, if there is reduced progression by 54% 2. Kidney Diseases-proteinuria is reduced by 54% 3. Neuropathies- risk is reduced by 60% • CSSI uses only rapid-acting insulin that provides a reproducible and predictable absorption • Use a single area for injection thus avoiding variations in absorption of body parts • Insulin does not accumulate in a subcutaneous depot, reducing the risk of mobilizing the deposit at a given moment and produce hypoglycemia. • better glycemic control while avoiding hypoglycemia night at dawn is obtained Patient selection is very important if you want to get the maximum effect of the insulin pump. The following characteristics should serve as a warning about who is not a good candidate for using the insulin pump: Child, adolescent or adult with poor family support. • Unwilling or unable to be monitored blood glucose three to four times a day. • Unwilling or unable to calculate how many meals. • Difficulty to calculate or adjust insulin doses, or to face difficulties with the pump. • Difficulty to follow instructions or comply with doctor visits. • Ashamed to be known diabetic and dependent on a mechanical device. • unstable psychiatric profile. <a id="

Several adjunctive technologies and tests are available for screening, surveillance, and risk stratification of Barrett esophagus (BE). The wide-area transepithelial sampling with three-dimensional analysis (WATS3D) is performed during the endoscopic examination of the esophagus, using a computer-assisted brush biopsy procedure as an adjunct to standard four-quadrant forceps biopsy. TissueCypher is a tissue systems pathology test that analyzes biopsy samples to predict the risk of progression to high-grade dysplasia or esophageal adenocarcinoma in patients with BE. EsoCheck is a non-endoscopic cell collection device used in conjunction with EsoGuard, a DNA methylation test, to detect BE and esophageal dysplasia. Esopredict is a DNA methylation assay that assesses the risk of progression to high-grade dysplasia or esophageal adenocarcinoma in patients with BE. These technologies and tests are intended to complement standard procedures in the screening, surveillance, and risk stratification of individuals with BE or at risk of developing BE.

Radioembolization (RE), also referred to as selective internal radiotherapy, delivers small beads (microspheres) impregnated with yttrium 90 intra-arterially via the hepatic artery. The microspheres, which become permanently embedded, are delivered to tumors preferentially because the hepatic circulation is uniquely organized, whereby tumors greater than 0.5 cm rely on the hepatic artery for blood supply while the normal liver is primarily perfused via the portal vein. Radioembolization has been proposed as a therapy for multiple types of primary and metastatic liver tumors.

Radioimmunoscintigraphy (RIS) involves the administration of radiolabeled monoclonal antibodies, which are directed against specific molecular targets, followed by imaging with an external gamma camera. Indium 111 capromab pendetide (ProstaScint) is a monoclonal antibody directed against a binding site on the prostate-specific membrane antigen. For individuals who have prostate cancer and are undergoing staging before curative treatment who receive RIS with indium 111 capromab pendetide, the evidence includes diagnostic accuracy studies and a systematic review (TEC Assessment). Relevant outcomes are overall survival, disease-specific survival, test accuracy, and test validity. For pretreatment staging before curative treatment, the TEC Assessment found that RIS has a modest sensitivity, estimated at 50% to 75%, and a moderate to high specificity, estimated at 72% to 93%. No studies have demonstrated that the use of RIS for pretreatment staging changes patient management or improves health outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals who have prostate cancer and have biochemical failure after curative treatment who receive RIS with indium 111 capromab pendetide, the evidence includes case series. Relevant outcomes are overall survival, disease-specific survival, test accuracy, and test validity. The available case series are generally retrospective, descriptive, and do not provide consistent verification of disease status. Thus, the studies do not permit accurate estimation of the false-positive and false-negative rates with RIS. There is a lack of published evidence demonstrating an association between RIS findings and change in patient management or health outcomes in this population of patients. The evidence is insufficient to determine the effects of the technology on health outcomes.

This evidence review addresses the use of magnetic resonance imaging (MRI) to monitor the integrity of silicone gel-filled breast implants (hereafter, referred to as silicone implants). For individuals who have suspected rupture of silicone breast implants who receive screening with MRI, the evidence includes diagnostic accuracy studies and systematic reviews. Relevant outcomes are test validity, morbid events, and treatment-related morbidity. The available literature on MRI for the detection of suspected rupture of silicone breast implants shows reasonable clinical validity, with high sensitivity and specificity when compared with the more invasive procedure of surgical explantation. While there is no direct evidence on the clinical utility of MRI for detecting suspected rupture, there is evidence for the clinical utility of confirming rupture prior to the explantation of an implant. Because other noninvasive techniques such as clinical examination, mammography, or ultrasonography have technical limitations and lower sensitivities and specificities, an MRI may be the most appropriate noninvasive diagnostic technique to confirm rupture. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. For individuals who are asymptomatic with silicone breast implants who receive screening with MRI, the evidence includes diagnostic accuracy studies and systematic reviews. Relevant outcomes are test validity, morbid events, and treatment-related morbidity. Studies of MRI screening for silent rupture in asymptomatic women with silicone implants have demonstrated reasonably high sensitivity and specificity compared with surgical explantation. However, the studies have generally been conducted in select populations (eg, women who want implants removed), and the data lack screening populations. None of the systematic reviews conducted pooled analyses that focused on asymptomatic women. Moreover, the clinical utility of MRI screening for silent rupture is unclear, ie, complications that may result from asymptomatic leakage of silicone are not well-characterized. The evidence is insufficient to determine the effects of the technology on health outcomes. <a id="

Using low-dose x-rays of 2 different energy levels, whole-body dual-energy x-ray absorptiometry (DXA) measures lean tissue mass, total and regional body fat, as well as bone density. DXA scans have become a tool for research on body composition (eg, as a more convenient replacement for underwater weighing). This evidence review addresses potential applications in clinical care rather than research use of the technology.

In individuals with heart failure, activation of the sympathetic nervous system is an early response to compensate for decreased myocardial function. The concentration of iodine 123 meta-iodobenzylguanidine (MIBG) over several hours after the injection of the agent is a potential marker of sympathetic neuronal activity. Iodine 123 meta-iodobenzylguanidine activity is proposed as a prognostic marker in individuals with heart failure to aid in the identification of individuals at risk of 1- and 2-year mortality. The marker could also be used to guide treatment decisions or to monitor the effectiveness of heart failure treatments.

Thermography is a noninvasive imaging technique that measures temperature distribution in organs and tissues. The visual display of this temperature information is known as a thermogram. Thermography has been proposed as a diagnostic tool for treatment planning and for evaluation of treatment effects for a variety of conditions.

Radiopharmaceuticals are composed of a radioisotope bond to an organic molecule and are used for diagnostic and therapeutic purposes. The organic molecule conveys the radioisotope to specific organs, tissues, or cells. Lutetium 177 (Lu 177) dotatate, classified as peptide receptor radionuclide therapy is a radiolabeled-somatostatin analogue that binds to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors such as neuroendocrine tumors. It is then internalized and beta particle emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive and neighboring cells.

Invasive coronary angiography (ICA) is clinically useful in stable ischemic heart disease when there is coronary artery obstruction that may benefit from revascularization. However, many individuals currently undergoing ICA will not benefit from revascularization. Therefore, if there are noninvasive alternatives to guide decisions about the use of ICA to spare individuals from unnecessary ICA, there is potential to improve health outcomes. Using noninvasive measurement of fractional flow reserve as part of a noninvasive imaging strategy may be beneficial to avoid the need for ICA.

Sacroiliac joint (SIJ) arthrography using fluoroscopic guidance with an injection of an anesthetic has been explored as a diagnostic test for SIJ pain. Duplication of the patient’s pain pattern with the injection of contrast medium suggests a sacroiliac etiology, as does relief of chronic back pain with an injection of local anesthetic. Treatment of SIJ pain with corticosteroids, radiofrequency ablation (RFA), stabilization, or minimally invasive SIJ fusion has also been explored.

Endobronchial ultrasound (EBUS) is an imaging technique for adjunctive use with standard flexible bronchoscopy. It provides an ultrasound-generated image of the lungs beyond the airway walls, extending to peribronchial structures and distal peripheral lung lesions. The purpose of EBUS is to facilitate navigation to distal regions of the lungs and biopsy of peripheral pulmonary nodules, especially suspected cancerous lesions. Another intended use of EBUS is to localize and facilitate biopsy of the mediastinal lymph nodes as part of staging for non-small-cell lung cancer. Both techniques primarily use transbronchial needle aspiration (TBNA) of lesions to obtain tissue samples.

Dopamine transporter imaging with single-photon emission computed tomography (DaT-SPECT), using radiopharmaceutical ioflupane injection, is a neuroimaging modality being evaluated to improve the differential diagnosis of parkinsonian syndromes from nonparkinsonian tremor, as well as dementia with Lewy bodies from Alzheimer disease.

Alzheimer disease (AD) is a fatal neurodegenerative disease that causes progressive loss in memory, language, and thinking, with the eventual loss of ability to perform social and functional activities in daily life. Because clinical diagnosis can be difficult, particularly early in the course of the disease or with atypical dementia, there has been considerable interest in developing biomarkers for AD that can be imaged through positron emission tomography (PET). Three radioactive tracers (florbetapir fluorine 18, florbetaben fluorine 18, flutemetamol fluorine 18) that bind to amyloid beta and can be detected in vivo with PET have been approved by the U.S. Food and Drug Administration (FDA) for amyloid beta imaging in patients who are being evaluated for cognitive decline. Amyloid beta plaque PET imaging is proposed as an adjunct to the clinical diagnosis of AD and as a component of identifying patients for amyloid beta plaque-targeting therapy. One radioactive tracer (flortaucipir F18) that binds to aggregated tau protein and can be detected in vivo with PET has been approved by the FDA for tau imaging in patients with cognitive impairment who are being evaluated for AD as an adjunct to the clinical diagnosis of AD and as a component of identifying patients for amyloid beta plaque-targeting therapy. Fluorine 18 fluorodeoxyglucose PET (FDG-PET) quantifies brain function by measuring glucose levels. FDG-PET is proposed as a method to distinguish AD from other dementias through identifying distinct regions of hypometabolism.

Digital breast tomosynthesis (DBT) uses modified digital mammography (DM) equipment to obtain additional radiographic data that are used to reconstruct cross-sectional "slices" of breast tissue. Tomosynthesis may improve the accuracy of DM by reducing distortions caused by overlapping tissue. Tomosynthesis typically involves additional imaging time and radiation exposure, although recent improvements may change this. For individuals who are asymptomatic and at average risk of breast cancer who receive 3-dimensional (3D) DBT as an adjunct to 2-dimensional (2D) mammography for screening, the evidence includes results from randomized controlled trials (RCTs), prospective observational studies, and retrospective observational studies. The relevant outcomes are overall survival, disease-specific survival, and test validity. There is a lack of direct evidence on the clinical utility of DBT from trials comparing health outcomes in patients screened using DBT and mammography. The available studies have provided limited data on interval cancers and follow-up of negative findings; however, available evidence would suggest that adding breast tomosynthesis to mammography may increase sensitivity and specificity of screening, potentially reducing the number of women who are recalled unnecessarily. Many studies had methodologic limitations, including inadequate follow-up of women with negative screening results, use of historical controls, and were based on screening practices in Europe that differ from those in the U.S. Preliminary results from the RETomo RCT would suggest an almost 90% increase in detection rate for mammography plus DBT compared with mammography alone with more instances of ductal carcinoma in situ with mammography plus DBT (+1 per 1000), benign lesions (+1 per 1000), and invasive cancers (+3 per 1000). The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals who are asymptomatic and at average risk of breast cancer who receive 3D DBT with synthesized 2D mammography for screening, the evidence includes preliminary results from an RCT, prospective observational studies, and retrospective observational studies. The relevant outcomes are overall survival, disease-specific survival, and test validity. The RCT reported similar cancer detection rates but lower recall rate for DBT plus synthesized DM. Two studies found higher detection rates with 3D DBT plus synthesized 2D mammography than with DM, one study found similar detection rates with 3D DBT plus synthesized 2D mammography compared with DM, and two found similar detection rates between 3D DBT plus synthesized 2D mammography and DBT plus DM. When comparing the recall rates of 3D DBT plus synthesized 2D mammography with DM alone, a prospective study found a higher recall rate in the former, a prospective study found similar rates, while retrospective studies had mixed findings. However, the potential for overdiagnosis (ie, diagnosis of cancer that would not cause symptoms during a patient's lifetime) cannot be ascertained because of the study designs, and interval cancer rates are not yet available. The studies lack long-term follow-up to assess false-negative results. Due to limitations in the studies, it is not possible to construct a chain of evidence. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals who have abnormal findings on breast imaging or clinical exam who receive 3D DBT as an adjunct to 2D mammography for diagnosis, the evidence includes multiple observational studies and a meta-analysis. The relevant outcomes are test validity and treatment-related morbidity. There is a lack of direct evidence on the clinical utility of DBT from diagnostic trials comparing health outcomes in patients diagnosed with breast cancer using DBT vs mammography. Mixed patient populations make it difficult to draw conclusions from the available studies on the diagnostic performance of DBT. Few prospective studies have addressed whether DBT improves diagnosis when added to mammography or mammography plus ultrasonography. Also, some concerns have been raised about the classification of microcalcification clusters with DBT alone. Due to limitations in the studies on diagnostic accuracy, it is not possible to construct a chain of evidence. The evidence is insufficient to determine the effects of the technology on health outcomes. <a id="

A Duplex scanning is a procedure of tracking by ultrasound that demonstrates the structures in two dimensions and in real time. It shows the blood speed in two directions with a spectral analysis, of the flow in color and its speed. To perform a Duplex scanning it is necessary to perform a scanning in real time, therefore the billing of a duplex scanning and Doppler ultrasound of the same part of the body represents "unbundling" and does not proceed for payment. The Duplex scanning should be limited to specific indications. The information required is anatomically accurate. Therefore, the Duplex scanning must not be used for situations in which another diagnostic study is 0recommended. <a id="

Noninvasive vascular studies of the upper and lower extremities veins are used primarily to establish the level or degree of obstructive disease and are necessary if there are findings and symptoms of this and / or the patient is a candidate for invasive treatment of their condition. There are two types of venous studies: • Physiological studies – these studies are functional measures including analysis of doppler waveform in response to compression segment, blood pressure measurements, pressure measurements of transcutaneous oxygen plethysmography volume segment determination provocation tests apply and determinations of reactive hyperemia. • The duplex scanning the upper and lower limbs is an ultrasonic scan where images and structures in two dimensions and in real time are shown, also it includes a spectral analysis with the blood flow velocity. <a id="

Non-invasive studies of the extracranial arteries consist of the direct and indirect use of ultrasound methods. The direct tests examine the anatomy and the physiology of the carotid artery while the indirect tests evaluate the hemodynamic changes of its distal branches (the orbital and brain circulation). Ultrasonography by Doppler evaluates the hemodynamic parameters particularly the speed of blood flow and the characteristics of the flow. This modality evaluates the supraorbital arteries, common carotid, external carotid, internal carotid and vertebral arteries of the neck. There are two types of peripheral arterial studies: · Physiological studies – these studies are of functional measures that include analysis of Doppler wave with response to the compression, measures of transcutaneous oxygen pressure or plethysmography. · A duplex scanning is an ultrasonic study where images and structures are shown in two dimensions and in real time. It also includes a spectral analysis with speed of blood flow. <a id="

Non-invasive studies of the arterial system of the upper and lower extremities are used primarily to establish the level or grade of obstructive arterial disease and is considered for payment if there are findings and symptoms of a possible ischemia of the extremity. It is also considered for payment if the patient is a candidate for invasive treatment of his condition. A history and physical examination that includes the ankle / brachial index can document the presence or absence of ischemic disease in most of the cases. They should not be used for the monitoring of the medical treatment (e.g. evaluation of pharmacological intervention). This latter case can be monitored with physical findings and/or progression or improvement of findings and symptoms. Edema rarely occurs in presence of occlusive disease except in its postoperative period, in association to an inflammatory process or associated to pain at rest. There are two types of peripheral arterial studies: Physiological studies – these studies are of functional measures that include analysis of Doppler wave form with response to the compression by segments, blood pressure measurements, measurements of transcutaneous oxygen pressure, plethysmography of volume by segments, determinations with provocation tests and reactive hyperemia determinations; Duplex scanning of the upper and lower extremities – is an ultrasonic scanning where images and structures are shown in two dimensions and in real time. It also includes a spectral analysis with the speed of the blood flow. <a id="

Optical coherence tomography is a noninvasive, high-resolution imaging method that can be used to visualize ocular structures. Optical coherence tomography of the anterior segment is being evaluated as a noninvasive diagnostic and screening tool for detecting angle-closure glaucoma, for presurgical evaluation, surgical guidance, and for assessing complications following surgical procedures. It is also being studied as a tool to evaluate the pathologic processes of dry eye syndrome, tumors, uveitis, and infections.

Positional magnetic resonance imaging (MRI) permits imaging of a patient in various positions, including sitting and standing. This technology is being evaluated as a diagnostic tool for patients with position-dependent back pain.

Positron emission tomography (PET) scans use positron-emitting radionuclide tracers, which simultaneously emit 2 high-energy photons in opposite directions. These photons can be simultaneously detected (referred to as coincidence detection) by a PET scanner, comprising multiple stationary detectors that encircle the thorax. Compared with single photon emission computed tomography (SPECT) scans, coincidence detection offers a greater spatial resolution. PET has been investigated as an option to diagnose and evaluate patients with cardiac conditions such as coronary artery disease, left ventricular dysfunction, and cardiac sarcoidosis.

Positron emission mammography (PEM) is a form of positron emission tomography that uses high-resolution, minicamera detection technology for imaging the breast. As with positron emission tomography, PEM provides functional rather than anatomic information about the breast. PEM has been studied primarily for use in presurgical planning and evaluation of breast lesions. For individuals who are being screened for breast cancer the evidence includes a retrospective study. Relevant outcomes are overall survival, disease-specific survival, test accuracy and validity, and resource utilization. It has not been demonstrated that PEM provides better diagnostic accuracy than the relevant comparators nor has PEM been shown to provide clinical utility. In addition, without demonstrated advantages in clinical utility, the relatively high radiation dosage associated with PEM does not favor its use given that alternative tests deliver lower doses. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with clinically localized breast cancer undergoing presurgical evaluation, the evidence includes prospective studies. Relevant outcomes are overall survival, disease-specific survival, test accuracy and validity, and resource utilization. It has not been demonstrated that PEM provides better diagnostic accuracy than the relevant comparators nor has PEM been shown to provide clinical utility. In addition, without demonstrated advantages in clinical utility, the relatively high radiation dosage associated with PEM does not favor its use given that alternative tests deliver lower doses. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with a suspicious breast lesion on conventional breast cancer evaluation, the evidence includes prospective studies as well as a meta-analysis. Relevant outcomes are overall survival, disease-specific survival, test accuracy and validity, and resource utilization. It has not been demonstrated that PEM provides better diagnostic accuracy than the relevant comparators nor has PEM been shown to provide clinical utility. In addition, without demonstrated advantages in clinical utility, the relatively high radiation dosage associated with PEM does not favor its use given that alternative tests deliver lower doses. The evidence is insufficient to determine the effects of the technology on health outcomes <a id="

Positron emission tomography (PET) scanning has many established roles in oncology. One potential use of PET scanning is to assess treatment response early in the course of therapy, with the intent of potentially altering the regimen based on PET scan results. While several types of PET scanning are used for interim detection of cancer, this review refers to fluorine 18 fluorodeoxyglucose positron emission tomography (FDG-PET) unless otherwise noted.

Magnetoencephalography (MEG) is a noninvasive functional imaging technique that records weak magnetic forces. When this information is superimposed on an anatomic image of the brain, typically a magnetic resonance imaging scan, the image is referred to as magnetic source imaging (MSI). MSI has been used to localize epileptic foci and to identify "eloquent" areas of the brain for neurosurgical planning. For individuals who have drug-resistant epilepsy and are being evaluated for possible resective surgery who receive MEG/MSI, the evidence for MEG/MSI as an adjunct to standard clinical workup includes various types of case series. Relevant outcomes are test accuracy and functional outcomes. Published evidence on MEG is suboptimal, with no clinical trials demonstrating clinical utility. The literature on diagnostic accuracy has methodologic limitations, primarily selection and ascertainment bias. Studies of functional outcomes do not fully account for the effects of MEG, because subjects who received MEG were not fully accounted for in the studies. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals who have a planned brain resection who require localization of eloquent function areas who receive MEG/MSI, the evidence includes comparative studies. Relevant outcomes include test accuracy and functional outcomes. Available studies have reported that this test has high concordance with the Wada test, which is currently the main alternative to localize eloquent functions. While management is changed in some patients based on MEG testing, it has not been demonstrated that these changes lead to improved outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes. Additional Information Clinical input obtained in 2011 supported the use of MEG/MSI for preoperative evaluation for resection brain surgery. Clinical input obtained in 2011 supported the use of MEG/MSI for localization of eloquent function areas. <a id="

Dynamic spinal visualization is a general term addressing different imaging technologies that simultaneously visualize spine (vertebrae) movements and external body movement. Vertebral motion analysis uses similar imaging as dynamic spinal visualization, with the addition of controlled movement and computerized tracking. These technologies have been proposed for the evaluation of spinal disorders including neck and back pain.

Computed tomography perfusion (CTP) imaging provides an assessment of cerebral blood flow that may help identify ischemic regions of the brain. This technology is proposed to aid treatment decisions in individuals being evaluated for acute ischemic stroke, subarachnoid hemorrhage (SAH), cerebral vasospasm, brain tumors, and head trauma.

Deep vein thrombosis (DVT) is a common occurrence. It is estimated that in the United States approximately 5 million patients experience one or more episodes of DVT each year, resulting in over 500,000 cases of pulmonary embolism and 100,000 deaths. Prompt treatment of acute thrombus is considered essential to initiate anticoagulation or thrombolytic therapy to prevent the serious consequences of pulmonary embolus. Radiographic evaluation of deep venous thrombus is performed both in symptomatic patients and in asymptomatic patients at high risk of venous thrombus, i.e., after orthopedic surgery. Contrast venography is considered the gold standard of diagnosis, but this invasive procedure is not routinely used. Duplex ultrasonography is probably the most common noninvasive technique used, followed by impedance plethysmography. Ultrasonography is thought to have excellent sensitivity and specificity in the thigh, but poor diagnostic accuracy below the knee. Both of the above techniques provide indirect evidence of thrombus by imaging an alteration in blood flow and thus cannot distinguish between acute and chronic thrombus. Direct detection of acute venous thrombus has been investigated using intravenously injected radiolabeled synthetic peptides that bind with high affinity to receptors expressed on activated platelets. In 1999, the FDA approved the radiopharmaceutical peptide apcitide (AcuTect™) for use in the scintigraphic imaging of acute venous thrombosis in the lower extremities in patients who have signs and symptoms of acute thrombophlebitis. Apcitide binds to glycoprotein IIb/IIIa fibrinogen receptors, which are expressed on the surface of activated platelets, thus making the radiopharmaceutical specific for acute, not chronic thrombus. <a id="

SPECT (Single photo emission computed tomography) is a radiological diagnostic test. Unlike CT, MRI that focuses on a part of the body, SPECT and PET offer information about the function of that part of the body. A radioactive material (2-fluoro-2-deoxy-D-glucose) is injected intravenously. This radioactive material is collected by the cells of the body in a different way depending on how the cell is functioning metabolically. This is why it is also known as Metabolic SPECT. A rotating chamber (gamma camera) records images of the signals emitted by the particles of the radioactive material injected and that has been located in a specific organ. A computer is fed by these series of images and they reconstruct in the form of planes, the organ studied. This study can determine myocardial viability. <a id="

Functional magnetic resonance imaging (fMRI) is a noninvasive method for localizing areas of brain function and has been used for the presurgical evaluation of eloquent brain areas. Using this method, images are collected while specific activities are performed to assist in the localization of critical cortical areas, as well as the evaluation of language lateralization. Functional MRI is also being investigated in combination with diffusion tensor imaging and electroencephalography to identify seizure focus. For individuals who have epilepsy or brain tumors who are undergoing presurgical mapping of the eloquent cortex who receive fMRI, the evidence includes studies on diagnostic accuracy and clinical utility. The relevant outcomes are test accuracy, morbid events, functional outcomes, and quality of life. The diagnostic accuracy of fMRI has been compared with the Wada test and intracortical mapping to evaluate postoperative language changes. Sensitivity and specificity depend on the specific task but have been shown to be predictive of hemispheric dominance in a substantial percentage of patients. According to findings from health outcomes, fMRI has several benefits for patients who are to undergo neurosurgery for seizures or brain tumors; these benefits are the potential to define eloquent areas (eg, controlling verbal or motor function), and the ability to reduce surgery time and alter treatment decisions. Because of the highly detrimental impact of resecting the eloquent cortex, fMRI may be considered complementary to the Wada test and direct electrical stimulation when the lesion is in close proximity to an eloquent area of the brain. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. For individuals who have epilepsy who are being evaluated for localization of seizure focus who receive simultaneous electroencephalography and fMRI, the evidence includes a limited number of small studies. The relevant outcomes are test accuracy, morbid events, functional outcomes, and quality of life. The objective of current research is to improve the identification of seizure focus with this technique, particularly when there are no interictal epileptic discharges during an fMRI session. There are very few data on the effect of this procedure on health outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes. Additional Information Not applicable.

Endoscopic ultrasonography (EUS) has evolved from a diagnostic imaging modality to one that can also be used for invasive diagnostic and therapeutic procedures. These advances are largely due to the introduction of linear scanning instruments that can be used to place devices into the ultrasound plane of view, permitting various interventions to be performed. The ability of EUS to guide a biopsy needle into lesions that are too small to be identified by computed tomography or magnetic resonance imaging, or too well encased by surrounding vascular structures to allow percutaneous biopsy, secures its role in a variety of clinical settings. Indications for EUS-guided fine-needle aspiration (EUS-FNA) include biopsy of mucosal and submucosal lesions in which prior conventional endoscopic biopsies have been nondiagnostic. The procedure is most commonly used to sample peri-intestinal structures such as lymph nodes and masses in the pancreas, liver, adrenal gland, and bile duct. It has also been used to aspirate peritoneal and pleural fluid. Endoscopic ultrasonography is used to establish the stages of tumors of the gastrointestinal track, pancreas and biliary ducts, being its main use to establish the stages of esophageal, gastric and rectal tumors. Some studies have shown that Endoscopic Sonography is the most exact imaging modality to determine the depth of the tumor invasion with a preoperative certainty between 80 to 90%, when compared with a histological specimen. Using ultrasound endoscopic sonography it cannot be distinguished with certainty whether the process is inflammatory or neoplastic. Likewise, ultrasonographic sonography has proved to be ineffective in determining the stages of lymphatic nodules, for the nodule had to be localized and identified as benign or malign. <a id="

Several types of fast computed tomography (CT) imaging, including electron-beam CT and spiral CT, allow the quantification of calcium in coronary arteries. Coronary artery calcium (CAC) is associated with coronary artery disease (CAD). The use of CAC scores has been studied in the prediction of future risk of CAD and in the diagnosis of CAD in symptomatic patients.

Vertebral fracture assessment (VFA) with densitometry is a technique to assess vertebral fractures at the same time as bone mineral density (BMD), using additional software with dual-energy x-ray absorptiometry (DXA). The addition of VFA to BMD may augment diagnostic information on fracture risk. Another method of determining vertebral fracture risk is biomechanical computed tomography (BCT), which evaluates both bone density and strength.

Contrast-enhanced coronary computed tomography angiography (CCTA) is a noninvasive imaging test that requires the use of intravenously administered contrast material and high-resolution, high-speed computed tomography machinery to obtain detailed volumetric images of blood vessels. It is a potential diagnostic alternative to current tests for cardiac ischemia (ie, noninvasive stress testing and/or coronary angiography).

Magnetic resonance angiography (MRA) is a technique for imaging vascular anatomy and pathology that does not use ionizing radiation. MRA is performed using magnetic resonance imaging (MRI) machines, and vascular images may be generated either with or without intravenous contrast agents, depending on the clinical application. However, the contrast agents used for MRA are associated with less risk of allergic reaction or nephrotoxicity than those used for conventional angiography. <a id="

Transcatheter intravascular ultrasound (IVUS) imaging is a technique in which a miniaturized ultrasound transducer, mounted on the tip of a catheter, is inserted directly into an artery or vein to produce either 2- dimensional tomographic images or 3-dimensional computer-assisted reconstructions of planar IVUS images. As applied to intracoronary imaging, intravascular ultrasound is used as an adjunct to angioplasty, atherectomy, or placement of a stent. Intracoronary Doppler ultrasound, which provides a functional measure of flow across a coronary lesion, is addressed separately in Policy No. 6.01.19.

Computer-aided detection (CAD) has been suggested as an adjunct to screening mammograms to decrease errors in perception, ie, failure to see an abnormality. The use of CAD systems requires a digital image, either generated by digitization of a prior screen-film mammogram (digitized mammogram), or generated directly (direct full-field digital mammogram). The effectiveness of CAD needs to be evaluated separately for these two types of digital images. Commercially available CAD systems use computerized algorithms for identifying suspicious regions of interest on the digital image. The locations of the abnormalities are marked such that the reader can then reference the same areas in the original mammogram for further review. The intent of CAD is to aid in detection of potential abnormalities for the radiologist to re-review. The radiologist, not CAD, makes the diagnosis if a clinically significant abnormality exists and whether future diagnostic evaluation is warranted. The distinction between digitized screen-film mammograms (SFM) and direct full-field digital mammograms (FFDM) is important. Since these two images are generated in different ways, the associated diagnostic performance of adjunctive CAD must be considered separately. Conceptually, the CAD systems used with digital mammography are very similar to those used with film mammography. The computer analyzes the digital images collected directly by the FFDM system, applies a set of algorithms that capture characteristics known to be associated potentially with malignancies, and produces an image with markings that show the site of suspicious findings. Sometimes, different marks are used for suspected masses and suspected microcalcifications. The major difference between CAD for FFDM and CAD for SFM is the extensive data set provided by the former and its interaction with the CAD algorithms. <a id="

Computed tomography colonography (CTC), also known as virtual colonoscopy, is an imaging modality that has been investigated as an alternative to conventional endoscopic ("optical") colonoscopy. It has been most widely studied as an alternative screening technique for colon cancer, and for the diagnosis of colorectal cancer (CRC) in people with related symptoms and for other colorectal conditions.

Percutaneous vertebroplasty, percutaneous balloon kyphoplasty, radiofrequency kyphoplasty, and mechanical vertebral augmentation are interventional techniques involving the fluoroscopically guided injection of polymethyl methacrylate into a weakened vertebral body or a cavity created in the vertebral body with a balloon or mechanical device. The techniques have been investigated to provide mechanical support and symptomatic relief in patients with osteoporotic vertebral compression fractures or those with osteolytic lesions of the spine (eg, multiple myeloma, metastatic malignancies); as a treatment for sacral insufficiency fractures; and as a technique to limit blood loss related to surgery.

Brachytherapy is a procedure in which a radioactive source (eg, radioisotope "seeds") is permanently or temporarily implanted in or near the tumor (eg, placed into the prostate gland to treat localized prostate cancer). The radiation from brachytherapy penetrates only short distances and is intended to deliver tumoricidal radioactivity directly to the tumor to improve local control while sparing surrounding normal tissue. Focal (subtotal) prostate brachytherapy is a form of organ-preserving therapy for small localized prostate cancers. This evidence review only assesses permanent low-dose rate (LDR) brachytherapy in prostate cancer.

Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) are 3-dimensional conformal radiotherapy methods that deliver highly focused, convergent radiotherapy beams on a target that is defined with 3-dimensional imaging techniques with the ability to spare adjacent radiosensitive structures. SRS primarily refers to such radiotherapy applied to intracranial lesions. SBRT refers to therapy generally applied to other areas of the body. Both techniques differ from conventional external-beam radiotherapy, which involves exposing large areas of tissue to relatively broad fields of radiation over multiple sessions.

Positron emission tomography (PET) scans are based on the use of positron-emitting radionuclide tracers coupled to organic 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, comprising multiple stationary detectors that encircle the area of interest. The utility of PET scanning for the diagnosis, staging and restaging, and surveillance of malignancies varies by type of cancer. In general, PET scanning can distinguish benign from malignant masses in certain circumstances and improve the accuracy of staging by detecting additional disease not detected by other imaging modalities. Therefore, PET scanning for diagnosis and staging of malignancies can be considered medically necessary when specific criteria are met for specific cancers, as outlined in the policy statements. For follow-up, after initial diagnosis and staging have been performed, there are a few situations in which PET can improve detection of recurrence, and lead to changes in management that improve the net health outcome. The use of PET for interim scanning to assess early response is addressed in policy 6.01.51.

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

Magnetic resonance imaging (MRI) of the breast is performed using scanners and intravenous imaging contrast agents in combination with specialized breast coils. This evidence review only addresses the use of breast MRI for clinical indications related to the detection or diagnosis of breast cancer as well as treatment planning.

Magnetic resonance spectroscopy (MRS) is a noninvasive technique that can be used to measure the concentrations of different chemical components within tissues. The technique is based on the same physical principles as magnetic resonance imaging (MRI) and the detection of energy exchange between external magnetic fields and specific nuclei within atoms.

Screening Mammogram A screening mammography is a radiologic procedure furnished to a woman without signs or symptoms of breast disease, for the purpose of early detection breast cancer,and includes a physician’s interpretation of the results of the procedure. For asymptomatic woman ages 50-74. Intervention of interest is Screening Mammography. Comparators of interest are other diagnostic and screening imaging available. Relevant outcomes include early detection and improvemnt of the net health outcome. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. Diagnostic Mammography A diagnostic mammography is a radiologic procedure furnished to a man or woman with signs and symptoms of breast disease, or a personal history of breast cancer, or a personal history of biopsy-proven benign breast disease, and includes a physician’s interpretation of the results of the procedure. For individuals with signs and symptoms of breast disease, or a personal history of breast cancer, or a personal history of biopsy-proven benign breast disease. Intervention of interest is Diagnostic Mammography. Comparators of interest are other diagnostic and screening imaging available. Relevant outcomes include early detection and improvemnt of the net health outcome. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. <a id="

Bone mineral density (BMD) studies can be used to identify individuals with osteoporosis and monitor response to osteoporosis treatment, with the goal of reducing the risk of fracture. Bone density is most commonly evaluated with dual x-ray absorptiometry (DXA); other technologies are available.

Magnetic resonance angiography (MRA) is the general term used to describe magnetic resonance imaging of vascular structures, but when MR is used to image a vein instead of an artery, the term “magnetic resonance venography” (MRV) may be used. The technical capabilities of current MRA make it most suitable for evaluation of large- and medium-sized vessels such as the thoracic aorta and major aortic branch vessels or the larger caliber central veins. MRA of the chest has the potential to replace angiography for some indications, thus eliminating its associated risk. In addition, MRA offers the unique ability to provide cross-sectional and projectional images of the vasculature in predictable orientations and easy-to-understand display formats without the use of contrast materials. This capability can facilitate planning of complex surgical procedures by simultaneously demonstrating the vascular anatomy of interest and displaying the anatomic interrelationships of these structures in three dimensions. MRA applications in the thorax can be subdivided into the following categories: · Acquired disease of the thoracic aorta; · Developmental anomaly of the thoracic vasculature; · Systemic venous thrombosis or occlusion; · Pulmonary embolism. <a id="

Most commonly, hemophilia is a recessive X-linked congenital bleeding disorder that predominantly affects males caused by deficiency of coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Deficiency or absence of clotting factor results in impaired hemostasis, prolonged bleeding, and rebleeding. Etranacogene dezaparvovec-drlb, fidanacogene elaparvovec-dzkt, and valoctocogene roxaparvovec-rvox are gene therapies designed to deliver a copy of the gene for the clotting factor using adeno-associated virus vector. Etranacogene dezaparvovec-drlb is designed to deliver a copy of the gene encoding the Padua variant of human coagulation factor IX (hFIX Padua) while fidanacogene elaparvovec-dzkt is designed to deliver a copy of human coagulation factor IX transgene modified to a high-specific factor IX activity variant known as FIX-R338L. Valoctocogene roxaparvovec-rvox is designed to deliver a functional copy of transgene encoding the B-domain deleted SQ form of human coagulation factor VIII.

Duchenne muscular dystrophy (DMD) is an inherited disorder that results in progressive muscle weakness and loss of muscle mass, primarily affecting males. DMD results from non-sense or frame-shifting variant(s) in the DMD gene, which is responsible for producing dystrophin, a cohesive protein essential for maintaining muscle support and strength. Delandistrogene moxeparvovec-rokl is an adeno-associated virus vector-based gene therapy which encodes a novel, engineered protein micro-dystrophin protein. This novel micro-dystrophin protein is a shortened version (138 kDa, compared to 427 kDa size of dystrophin expressed in normal muscle cells) that contains selected domains of dystrophin expressed in normal muscle cells.

Metachromatic leukodystrophy (MLD) is a rare autosomal recessive lysosomal storage disorder. It arises due to biallelic pathogenic variants in the arylsulfatase A(ARSA) gene, which leads to a deficiency of the lysosomal ARSA enzyme. This enzyme plays a crucial role in metabolizing sulfatides, a major component of myelin membranes in both the central and peripheral nervous system. When ARSA is deficient, undegraded sulfatides accumulate within the central and peripheral nervous system causing microglial damage, progressive demyelination, neurodegeneration, and ultimately resulting in the loss of motor and cognitive functions, often leading to early death –especially in patients with symptom onset before the age of 7 years. MLD subtypes are primarily defined based on age of symptom onset. The late infantile subtype is defined by symptom onset before 30 months of age while early juvenile subtype is defined by symptom onset between 30 months and 7 years of age. In late juvenile subtype, symptom onset is between 7 years and 16 years of age. Symptom onset after 16 years of age is defined as adult onset. Late infantile and early juvenile are the most severe subtypes. Prior to the approval of atidarsagene autotemcel, there were no approved treatments for MLD in the US. Allogeneic hematopoietic stem cell transplantation has shown benefit in some patients with late-onset MLD who are pre-symptomatic or minimally symptomatic at the time of transplant, but it offers little or no benefit in patients with late infantile or early juvenile MLD. Atidarsagene autotemcel is an autologous hematopoietic stem cell (HSC)-based gene therapy which adds functional copies of the ARSA gene into patients’ HSCs through transduction of autologous CD34+ cells with Lenti-D lentiviral vector. The genetically repaired cells are infused back into the individual, where, once engrafted, they differentiate into multiple cell types, some of which migrate across the blood-brain barrier into the central nervous system and express the functional enzyme.

Sickle cell disease is a genetic hemoglobinopathy that results from a genetic variant in the HBB gene resulting in the production of dysfunctional hemoglobin which forms polymers in the red blood cells of individuals. The sickled red blood cells have a shorter life span and do not move as freely as normal, round, red blood cells resulting in anemia and vascular obstruction. Recurrent acute pain crises, or vaso-occlusive crises are the most prevalent manifestation of sickle cell disease. It is estimated that there are 100,000 individuals living with sickle cell disease in the United States. Two gene therapies have been approved by the U.S. Food and Drug Administration. Lovotibeglogene autotemcel adds functional copies of a modified βA-globin gene (βA-T87Q-globin) into an individual's hematopoietic stem cell through transduction of autologous CD34+ cells with BB305 lentiviral vector. After infusion, the transduced CD34+ hematopoietic stem cells engraft in the bone marrow and differentiate to produce red blood cells containing βA-T87Q gene that will produce HbAT87Q protein (functional gene therapy-derived hemoglobin). Exagamglogene autotemcel is a cellular gene therapy consisting of autologous CD34+ hematopoietic stem cells edited by CRISPR/Cas9-technology at the erythroid specific enhancer region of the BCL11A gene to reduce BCL11A expression in erythroid lineage cells. After infusion, the edited CD34+ cells engraft in the bone marrow and differentiate to erythroid lineage cells with reduced BCL11A expression. Reduced BCL11A expression results in an increase in γ-globin expression and fetal hemoglobin protein production in erythroid cells.

Beta (β)-thalassemia is a genetic hemoglobinopathy that results from defects in β-globin synthesis leading to reduced synthesis or absence of β-globin chains causing impaired production of hemoglobin. The clinical presentation is that of anemia which requires transfusion and multiple downstream sequelae from iron overload. It is estimated that at least 1000 people in the United States have transfusion-dependent β-thalassemia. Betibeglogene autotemcel contains autologous CD34+ hematopoietic stem cells in which functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) have been added. Once the hematopoietic stem cells reengineered with βA-T87Q are infused, they engraft in the bone marrow and differentiate to produce red blood cells containing βA-T87Q gene that will produce HbAT87Q protein (functional gene therapy-derived hemoglobin) at levels that may eliminate or significantly reduce the need for transfusions. Exagamglogene autotemcel is a cellular gene therapy consisting of autologous CD34+ hematopoietic stem cells edited by CRISPR/Cas9-technology at the erythroid specific enhancer region of the BCL11A gene to reduce BCL11A expression in erythroid lineage cells. After infusion, the edited CD34+ cells engraft in the bone marrow and differentiate to erythroid lineage cells with reduced BCL11A expression. Reduced BCL11A expression results in an increase in γ-globin expression and fetal hemoglobin protein production in erythroid cells.

Multiple myeloma is a hematologic malignancy characterized by abnormal growth of plasma cells with production of abnormal proteins instead of typical antibodies. Plasma cell proliferation in the marrow causes bone pain and fractures due to lytic lesions and displaces other marrow cellular elements. An increase in total or monoclonal proteins can have direct toxic effects on the kidney, resulting in worsening renal function, hypercalcemia, and anemia. Treatment of multiple myeloma includes immunomodulatory agents (thalidomide, lenalidomide, or pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, or ixazomib), and anti-CD38 monoclonal antibodies (daratumumab or isatuximab). While multiple combinations of these agents can lead to remission, most patients eventually relapse. Idecabtagene vicleucel and ciltacabtagene autoleucel are B-cell maturation antigen (BCMA) targeting chimeric antigen receptor (CAR) T-cell therapies for the treatment of individuals with relapsed and/or refractory multiple myeloma who have received at least 4 prior therapies.

Tofersen (Qalsody) is an antisense oligonucleotide indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain observed in pati ents treated with tofersen (Qalsody). Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial. Amyotrophic lateral sclerosis (ALS) is a debilitating disease caused by degeneration of cortical, brainstem, and spinal cord motor neurons and, in some cases, frontotemporal cortical neurons. The neurodegeneration results in progressive muscle weakness, muscle spasticity, dysarthria, dysphagia, cognitive and behavioral impairments, and other motor symptoms. <a id="

Hematologic malignancies are a heterogeneous group of diseases characterized by distinct biological subtypes, marked by cellular, immunophenotypic, and genetic profile variations. Therapeutic approaches may involve hematopoietic cell transplantation, and in cases where a suitable matched donor is unavailable, umbilical cord blood may serve as a source of hematopoietic stem and progenitor cells for transplantation. Ex vivo expansion strategies using nicotinamide have been investigated to expedite hematopoietic recovery and enhance cell volume without inducing differentiation or cellular stress commonly associated with culturing hematopoietic progenitor cells outside their natural environment. Omidubicel is a modified allogeneic hematopoietic progenitor cell therapy derived from cord blood utilizing a proprietary nicotinamide enrichment technology.

Acute hepatic porphyria (AHP) is a rare disease with a prevalence of 5 to 10 cases/100,000 people in the US and effects primarily females (age range 15 to 45 years). The induction of the enzyme aminolevulinate synthase 1 (ALAS1) results in increased production and accumulation of toxic heme intermediates delta aminolevulinic acid and porphobilinogen in the plasma and urine. The accumulation of these toxic heme intermediates results in acute attacks characterized by severe abdominal pain, muscle weakness, seizures, psychiatric dysfunction, irreversible neurologic damage, and increased risk of hepatic malignancy. Givosiran (Givlaari®) is a double-stranded small interfering RNA that causes degradation of ALAS1 mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to decreased circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of acute hepatic porphyria.

Myasthenia gravis is an autoimmune neuromuscular disorder characterized by fluctuating motor weakness involving ocular, bulbar, limb, and/or respiratory muscles. The weakness is due to an antibody-mediated, immunologic attack directed at proteins in the postsynaptic membrane of the neuromuscular junction (acetylcholine receptors or receptor-associated proteins). Eighty to 90 percent of individuals with myasthenia gravis have autoantibodies against the acetylcholine receptor detectable in serum, and these antibodies are believed to play a central role in disease pathomechanism. Eculizumab (Soliris®), eculizumab-aeeb (Bkemv®), eculizumab-aagh (Epysqli®) and ravulizumab-cwvz (Ultomiris®) are monoclonal antibodies that are presumed to exert a therapeutic effect in individuals with generalized myasthenia gravis through the reduction of terminal complement complex C5b-9 deposition at the neuromuscular junction. Efgartigimod alfa-fcab (Vyvgart®) is a human IgG1 antibody fragment that binds to the neonatal Fc receptor, resulting in the reduction of circulating IgG in individuals with generalized myasthenia gravis. Vygart Hytrulo is a coformulation of efgartigimod alfa and hyaluronidase (human recombinant) which can be administered subcutaneously. The addition of hyaluronidase increases the dispersion and absorption of co-administered drugs when administered subcutaneously. Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor resulting in the reduction of circulating IgG.

Alzheimer disease (AD) is a neurodegenerative disorder leading to progressive, irreversible destruction of neurons and loss of cognitive function and memory. Over time, patients progress to severe dementia, loss of independence, and death. Extracellular deposits of amyloid beta, referred to as amyloid plaques, are considered a hallmark of the disease. Beta-amyloid monomers lead to formation of beta oligomers and fibrils, are deposited as plaques, and then interact with tau fibrils, leading to formation of neuro-fibrillatory tangles. These pathophysiological changes and clinical manifestations of AD are progressive and occur along a continuum, and accumulation of amyloid beta may begin 20 years or more before symptoms arise. Two monoclonal antibodies (aducanumab and lecanemab) have been approved by the U.S. Food and Drug Administration under accelerated approval based on the reduction in amyloid beta plaques. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.

Primary hyperoxalurias are a group of rare genetic diseases. There are 3 subtypes each resulting in the overproduction of oxalate by the liver. Type 1 is the most common type, which accounts for approximately 80% of cases and occurs as a result of a genetic defect in the alanine:glyoxylate aminotransferase (AGXT) gene that encodes the enzyme alanine glyoxylate aminotransferase. Defect in the enzyme results in overproduction of oxalate, which leads to deposition of calcium oxalate crystals in the kidneys and urinary tract. The result is the formation of painful and recurrent nephrolithiasis (renal stones), nephrocalcinosis, and renal failure. Compromised renal function exacerbates the disease as the excess oxalate can no longer be effectively excreted, resulting in subsequent accumulation and crystallization in bones, eyes, skin, and heart, leading to severe illness and death. Lumasiran is a subcutaneously administered RNA interference (RNAi) therapeutic that silences the HAO1 gene, which encodes for a glycolate oxidase enzyme. By silencing the HAO1 gene, levels of glycolate oxidase are depleted, decreasing production of oxalate, the metabolite that directly contributes to the pathophysiology of primary hyperoxaluria type 1.

Polivy® (polatuzumab vedotin-piiq) is an antibody-drug conjugate directed against CD79b. It is FDA-approved in combination regimens for adult patients with diffuse large B-cell lymphoma (DLBCL) <a id="

Hematopoietic Colony-Stimulating Factors (CSFs) are biologic agents used to stimulate the production of neutrophils and reduce the incidence of febrile neutropenia in patients undergoing cytotoxic chemotherapy. Their use has been shown to decrease hospitalization rates, treatment-related complications, and improve patient quality of life. Multiple CSFs are available, including filgrastim, pegfilgrastim, and tbo-filgrastim, as well as biosimilars. Several brands of short-acting colony-stimulating factors (CSFs) are available, including Neupogen® (filgrastim), Zarxio® (filgrastim-sndz), Nivestym® (filgrastim-aafi), Granix® (tbo-filgrastim), and Leukine® (sargramostim). There is no reliable evidence that any one short-acting CSF brand is superior to another for medically necessary indications. Long-acting granulocyte colony-stimulating factors (G-CSFs) include Neulasta® (pegfilgrastim), Neulasta Onpro® kit (pegfilgrastim), Nyvepria® (pegfilgrastim-apgf), Fulphila® (pegfilgrastim-jmdb), Udenyca® (pegfilgrastim-cbqv), and Ziextenzo® (pegfilgrastim-bmez). Evidence similarly shows no clinically meaningful differences in efficacy or safety between available pegfilgrastim products. <a id="

Esketamine is the S-isomer of racemic ketamine. Esketamine targets the N-methyl-D-aspartate receptor, an ionotropic glutamate receptor in nerve cells. However, the mechanism by which esketamine exerts its antidepressant effect is unknown. It is currently approved for individuals with treatment-resistant depression as monotherapy or in conjunction with an oral antidepressant or for major depressive disorder with acute suicidal ideation or behavior in conjunction with an oral antidepressant.Treatment-resistant depression is chronic depression that does not improve despite the adequate use of multiple antidepressants. The poor response to multiple antidepressants limits additional treatment options. Individuals with major depressive disorder who have active suicidal ideation with intent constitute a psychiatric emergency as the time between the onset of suicidal ideation and suicide attempt is often very short. While standard antidepressants effectively treat depressive symptomatology, including suicidal ideation, these agents require 4 to 6 weeks to exert their full effect, limiting their utility in crisis situations.

Clostridial collagenase is a bacterial collagenase, derived from Clostridium histolyticum, which has been evaluated for the treatment of fibroproliferative disorders such as Dupuytren's contracture, Peyronie's disease, and adhesive capsulitis.

Repository corticotropin injection is a preparation of the natural form of adrenocorticotropic hormone (ACTH). The injection is used to treat corticosteroid-responsive conditions and as a diagnostic tool to test adrenal function.