Multiscale cardiac imaging spanning the whole heart and its internal cellular architecture in a small animal model.

Cardiac pumping depends on the morphological structure of the heart, but also on its subcellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of technologies that can image the three-dimensional (3D) heart structure, to assess malformations; and its ultrastructure, to assess organelle disruptions. We present here a multiscale, correlative imaging procedure that achieves high-resolution images of the whole heart, using 3D micro-computed tomography (micro-CT); and its ultrastructure, using 3D scanning electron microscopy (SEM). In a small animal model (chicken embryo), we achieved uniform fixation and staining of the whole heart, without losing ultrastructural preservation on the same sample, enabling correlative multiscale imaging. Our approach enables multiscale studies in models of congenital heart disease and beyond.

The heart is our hardest-working organ and beats around 100,000 times a day, pumping blood through a vast system of vessels to all areas of the body. Specialized heart cells make the heart contract rhythmically, enabling it to work efficiently. Contractile molecules inside these cells, called myofibrils, align within the heart cells, and heart cells align to each other, so that the heart tissue contracts effectively. However, when the heart has defects or is diseased this organization can be lost, and the heart may no longer pump blood efficiently, leading to sometimes life-threatening complications. For example, around one in a hundred newborn babies suffer from congenital heart defects, and despite medical advances, these conditions remain the main cause of non-infectious mortality in children. Many cases of congenital heart disease are diagnosed before a baby is born during an ultrasound scan. However, these scans, as well as subsequent diagnostic tools, lack the precision to detect problems within the heart cells. Now, Rykiel et al. used two complementary imaging techniques known as micro-computed tomography and scanning electron microscopy to acquire pictures of the whole heart as well as of the organization inside the heart cells. This made it possible to capture the structure of the heart tissue at both micrometer (the whole heart) and nanometer resolution (the inside of the cells), and to study what happens within the heart and its cells when the heart has a defect. Rykiel et al. tested the imaging technology on the hearts of chicken embryos, at stages equivalent to a five to six-month-old human fetus, and compared a healthy heart with a heart with a defect called tetralogy of Fallot. They found that the tissues in the heart with a defect had a sponge-like appearance, with increased space in between cells. Moreover, the myofibrils of the heart with a defect were aligned differently compared to those in the normal heart. More research is needed to fully understand what happens when the heart has a defect. However, the imaging technology used in this study offers the possibility of examining the heart at an unprecedented level of detail. This will deepen our understanding of how structural heart defects arise and how they affect the pumping of the heart, and will give us clues to design better treatments for patients with heart defects and other heart anomalies.

ACR Appropriateness Criteria Low Back Pain.

Most patients presenting with uncomplicated acute low back pain (LBP) and/or radiculopathy do not require imaging. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags raising suspicion for serious underlying conditions, such as cauda equina syndrome, malignancy, fracture, and infection. Many imaging modalities are available to clinicians and radiologists for evaluating LBP. Application of these modalities depends largely on the working diagnosis, the urgency of the clinical problem, and comorbidities of the patient. When there is concern for fracture of the lumbar spine, multidetector CT is recommended. Those deemed to be interventional candidates, with LBP lasting for > 6 weeks having completed conservative management with persistent radiculopathic symptoms, may seek MRI. Patients with severe or progressive neurologic deficit on presentation and red flags should be evaluated with MRI. The ACR 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 (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria Osteonecrosis of the Hip.

Osteonecrosis of the hip (Legg-Calvé-Perthes) is a common disease, with 10,000-20,000 symptomatic cases annually in the United States. The disorder affects both adults and children and is most frequently associated with trauma and corticosteroid usage. The initial imaging evaluation of suspected hip osteonecrosis is done using radiography. MRI is the most sensitive and specific imaging modality for diagnosis of osteonecrosis of the hip. The clinical significance of hip osteonecrosis is dependent on its potential for articular collapse. The likelihood of articular collapse is significantly increased with involvement of greater than 30%-50% of the femoral head area, which is optimally evaluated by MRI, often in the sagittal plane. Contrast-enhanced MRI may be needed to detect early osteonecrosis of the hip in pediatric patients, revealing hypoperfusion. In patients with a contraindication for MRI, use of either CT or bone scintigraphy with SPECT (single-photon emission CT) are alternative radiologic methods of assessment. Imaging helps guide treatment, which may include core decompression, osteotomy, and ultimately, need for joint replacement. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every three 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Follow-Up of Malignant or Aggressive Musculoskeletal Tumors.

Appropriate imaging modalities for the follow-up of malignant or aggressive musculoskeletal tumors include radiography, MRI, CT, (18)F-2-fluoro-2-deoxy-D-glucose PET/CT, (99m)Tc bone scan, and ultrasound. Clinical scenarios reviewed include evaluation for metastatic disease to the lung in low- and high-risk patients, for osseous metastatic disease in asymptomatic and symptomatic patients, for local recurrence of osseous tumors with and without significant hardware present, and for local recurrence of soft tissue tumors. The timing for follow-up of pulmonary metastasis surveillance is also reviewed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Myelopathy.

Patients presenting with myelopathic symptoms may have a number of causative intradural and extradural etiologies, including disc degenerative diseases, spinal masses, infectious or inflammatory processes, vascular compromise, and vertebral fracture. Patients may present acutely or insidiously and may progress toward long-term paralysis if not treated promptly and effectively. Noncontrast CT is the most appropriate first examination in acute trauma cases to diagnose vertebral fracture as the cause of acute myelopathy. In most nontraumatic cases, MRI is the modality of choice to evaluate the location, severity, and causative etiology of spinal cord myelopathy, and predicts which patients may benefit from surgery. Myelopathy from spinal stenosis and spinal osteoarthritis is best confirmed without MRI intravenous contrast. Many other myelopathic conditions are more easily visualized after contrast administration. Imaging performed should be limited to the appropriate spinal levels, based on history, physical examination, and clinical judgment. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Acute Trauma to the Knee.

More than 500,000 visits to the emergency room occur annually in the United States, for acute knee trauma. Many of these are twisting injuries in young patients who can walk and bear weight, and emergent radiographs are not required. Several clinical decision rules have been devised that can considerably reduce the number of radiographs ordered without missing a clinically significant fracture. Although a fracture is seen on only 5% of emergency department knee radiographs, 86% of knee fractures result from blunt trauma. In patients with a fall or twisting injury who have focal tenderness, effusion, or inability to bear weight, radiographs should be the first imaging study obtained. If the radiograph shows no fracture, MRI is best for evaluating for a suspected meniscus or ligament tear, or the injuries from a reduced patellar dislocation. Patients with a knee dislocation should undergo radiographs and an MRI, as well as an angiographic study such as a fluoroscopic, CT, or MR angiogram. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Acute Trauma to the Foot.

This ACR Appropriateness Criteria article offers imaging triage guidance for several variants of patients presenting with acute foot trauma. Patients meeting inclusion criteria for the Ottawa Rules should undergo a 3-view radiographic series. Diabetic patients with peripheral neuropathy should undergo radiography, even though they do not meet the Ottawa Rules inclusion criteria. Patients with suspected midfoot and/or Lisfranc injury should undergo 3-view radiographs with weight bearing on at least the anterior-posterior view. Patients with suspected Lisfranc injury and normal radiographs should be considered for MRI and CT on a case-by-case basis. MRI or ultrasound could confirm cases of suspected acute tendon rupture. Radiography is the initial imaging modality for suspected plantar plate injury after metatarsal-phalangeal joint injury. Weight-bearing anterior-posterior, lateral, and sesamoid axial views may detect proximal migration of the hallux sesamoids. Ultrasound or MRI can directly evaluate the capsuloligamentous complex, specifically the plantar plate. Radiography can detect radiopaque penetrating foreign bodies, and ultrasound can be helpful in detecting those that are nonradiopaque. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 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 instances in which evidence is lacking or is not definitive, expert opinion may be used to recommend imaging and treatment.

ACR Appropriateness Criteria acute trauma to the ankle.

Acute ankle injuries are frequently diagnosed and treated in emergency departments and outpatient clinics. Recent evidence-based clinical treatment guidelines and systematic review of economic analyses support the use of 3-view (anteroposterior, lateral, and mortise) radiographic evaluation of patients meeting the criteria of the Ottawa ankle rules. Cross-sectional imaging has a limited secondary role primarily as a tool for preoperative planning and as a problem-solving technique in patients with persistent symptoms and suspected of having occult fractures. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR appropriateness criteria management of vertebral compression fractures.

This is an updated review of management of vertebral compression fracture for both benign osteoporotic and malignant causes. Vertebral compression fracture radiologic imaging evaluation is discussed. A literature review is provided of current indications for vertebral augmentation with percutaneous vertebroplasty and kyphoplasty as well as medical management. Limitations and potential benefits of these procedures are discussed. Variant tables describing various clinical situations are also provided to assist in determining appropriate use of these treatments for patient care. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 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 in which evidence is lacking or not definitive, expert opinion may be used to formulate recommendations for imaging or treatment.

ACR appropriateness criteria acute hip pain-suspected fracture.

Substantial cost, morbidity, and mortality are associated with acute proximal femoral fracture and may be reduced through an optimized diagnostic imaging workup. Radiography represents the primary diagnostic test of choice for the evaluation of acute hip pain. In middle aged and elderly patients with negative radiographs, the evidence indicates MRI to be the next diagnostic imaging study to exclude a proximal femoral fracture. CT, because of its relative decreased sensitivity, is only indicated in patients with MRI contraindications. Bone densitometry (DXA) should be obtained in patients with fragility fractures. 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.

ACR appropriateness criteria(®) acute trauma to the knee.

There are more than 1 million visits to the ER annually in the United States for acute knee trauma. Many of these are twisting injuries in young patients who can walk and bear weight, and emergent radiography is not required. Several clinical decision rules have been devised that can considerably reduce the number of radiographic studies ordered without missing a clinically significant fracture. Although fractures are seen on only 5% of emergency department knee radiographs, 86% of knee fractures result from blunt trauma. In patients with falls or twisting injuries who have focal tenderness, effusion, or inability to bear weight, radiography should be the first imaging study performed. If radiography shows no fracture, MRI is best for evaluating for a suspected meniscal or ligament tear or patellar dislocation. Patients with knee dislocation should undergo radiography and MRI, as well as fluoroscopic angiography, CT angiography, or MR angiography. 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® on acute shoulder pain.

The shoulder joint is a complex array of muscles, tendons, and capsuloligamentous structures that has the greatest freedom of motion of any joint in the body. Acute (<2 weeks) shoulder pain can be attributable to structures related to the glenohumeral articulation and joint capsule, rotator cuff, acromioclavicular joint, and scapula. The foundation for investigation of acute shoulder pain is radiography. Magnetic resonance imaging is the procedure of choice for the evaluation of occult fractures and the shoulder soft tissues. Ultrasound, with appropriate local expertise, is an excellent evaluation of the rotator cuff, long head of the biceps tendon, and interventional procedures. Fluoroscopy is an excellent modality to guide interventional procedures. Computed tomography is an excellent modality for characterizing complex shoulder fractures. Computed tomographic arthrography or fluoroscopic arthrography may be alternatives in patients for whom MR arthrography is contraindicated. A multimodal approach may be required to accurately assess shoulder pathology. 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR appropriateness criteria on metastatic bone disease.

Appropriate imaging modalities for screening, staging, and surveillance of patients with suspected and documented metastatic disease to bone include (99m)Tc bone scanning, MRI, CT, radiography, and 2-[(18)F]fluoro-2-deoxyglucose-PET. Clinical scenarios reviewed include asymptomatic stage 1 breast carcinoma, symptomatic stage 2 breast carcinoma, abnormal bone scan results with breast carcinoma, pathologic fracture with known metastatic breast carcinoma, asymptomatic well-differentiated and poorly differentiated prostate carcinoma, vertebral fracture with history of malignancy, non-small-cell lung carcinoma staging, symptomatic multiple myeloma, osteosarcoma staging and surveillance, and suspected bone metastasis in a pregnant patient. No single imaging modality is consistently best for the assessment of metastatic bone disease across all tumor types and clinical situations. In some cases, no imaging is indicated. The recommendations contained herein are the result of evidence-based consensus by the ACR Appropriateness Criteria((R)) Expert Panel on Musculoskeletal Radiology.