Nuclear Medicine Musculoskeletal Assessment, Protocols, and Interpretation

The use of radioactive substances in evaluating the musculoskeletal system has a relatively long history. Early researchers explored the metabolic activity of bone using phosphorus-32 and autoradiography. Further research explored the uptake of radiogallium by various skeletal tissues, including bone tumors, and demonstrated increased uptake before radiographic changes were visible. In 1971, 99mTc 99m polyphosphate was introduced as a readily available and inexpensive bone scanning agent. This became the basis of many tracers, including 99mTc-methylene diphosphonate and hydroxymethylene diphosphonate. Bone scan, or bone scintigraphy, uses radiopharmaceuticals consisting of a radionuclide bound to members of the phosphate family, the most common form being 99mTc-methylene diphosphonate (99mTc-MDP). Bone scintigraphy is exquisitely sensitive to bone turnover, detecting as little as a 5% change. In specific instances, this can provide evidence of bone disease or dysfunction before bony changes are appreciated on conventional radiography.  Uptake can be seen with multiple conditions, including fracture, malignancy, and infection. Other disorders of bone turnover can also be seen, such as fibrous dysplasia and avascular necrosis. Certain scan phases can show soft tissue conditions such as cellulitis and complex regional pain syndrome. "Cold spots" may be caused by areas of decreased bone turnover seen with certain tumors and bone abscesses or caused by decreased blood flow, such as in frostbite, gangrene, or avascular necrosis.  Single-photon emission computed tomography (SPECT), which can also be combined with conventional CT images (SPECT/CT), is an adjunct to bone scintigraphy and typically allows for more accurate anatomic localization of lesions. Gallium-67 citrate emerged as one of the earliest tracers in musculoskeletal tumor and infection imaging. It was commonly used with bone scintigraphy, and results are based on the uptake patterns of the 2 tracers. Gallium-67 imaging is a well-established modality with a 65 to 80% sensitivity for osteomyelitis when combined with bone scintigraphy. This radionuclide has a half-life of 78 hours, requiring a 2 to 3-day delay between administration and imaging, making imaging logistically difficult. Ga-67, in combination with SPECT, is currently used to diagnose spondylodiscitis, although more recent literature suggests the superiority of fluorine-18 2'-deoxy-2-fluoro-D-glucose PET (FDG/PET) scans in this indication. Gallium-67 is currently infrequently used.  The radiolabeling of leukocytes to localize musculoskeletal infection has been used for the past 3 decades with great success. Indium-111 and 99mTc labeled hexamethylpropylene amine oxime (99mTc-HMPAO) are the most commonly used radiotracers. There are several differences between the 2 isotopes used for labeled leukocyte scintigraphy. The advantages of Indium-111 are a limited normal distribution and stability of the label, which allows delayed imaging. 99mTc-HMPAO, in contrast, has a large normal distribution, including liver, lungs, spleen, gastrointestinal system, and urinary tract, but offers higher resolution images. Radiation exposure to the patient is significantly lower when using 99mTc-HMPAO. Variability in intramedullary bone marrow distribution from fractures or hardware can lead to difficulty differentiating infection from normal active marrow when investigating infection of the bone. In these instances, utilizing a 99mTc-Sulfur Colloid scan can differentiate the two. Both labeled leukocytes and 99mTc-sulfur colloid show activity in the normal bone marrow. Still, infection changes the intraosseous environment so that 99mTc-sulfur colloid is not taken up by phagocytes and is cleared from the marrow in these areas, therefore showing no activity in areas of infection.  The test is positive when the labeled white blood cell scan shows activity absent on the 99mTc-sulfur colloid scan. Drawbacks to leukocyte scintigraphy include delayed results and in-vitro blood handling for the labeling process, described in more detail below.  Positron emission tomography (PET) is a nuclear medicine imaging modality that uses 18-F fluorodeoxyglucose (FDG) as a tracer. It is based on the detection of photons that are produced during radionuclide decay. Positrons are emitted from the nucleus of the radionuclide during decay, producing 2 annihilation photons, which are detected by the scanner. After administration, the tracer enters cells by glucose transporters (GLUTs) and is phosphorylated to FDG-6-phosphate. Uptake is primarily dependent on glucose transporter concentration and cellular metabolic activity. FDG-6-phosphate cannot be further metabolized in the glycolytic pathway and accumulates in the cell.  Glucose-6-phosphatase normally dephosphorylates FDG, allowing it to leave the cell. Tumor cells commonly exhibit decreased glucose-6-phosphatase concentrations, which may cause cells to retain tracer for longer periods, leading to detection using the delayed scan technique.  FDG is a nonspecific tracer, showing uptake in many tissues with increased glucose transporters, such as the muscles, heart, GI tract, urinary tract, and brain. Uptake in other organs and the bony skeleton is normally low. Normal bone marrow does not exhibit significant uptake; therefore, active inflammatory infiltrates can be easily distinguished from hematopoietic marrow. States of active inflammation show increased uptake due to the increased concentration of glucose transporters in active inflammatory cells. FDG-PET provides some advantages to other forms of nuclear musculoskeletal imaging. It provides prompt results, typically around 2 hours after tracer injection. It is not distorted or affected by metal implants and offers a relatively high resolution of 4 to 5 mm. In the form of PET/CT, 3-dimensional localization and anatomic correlation improve.