1. NM 4203 Scanning & Imaging Skeletal System

2. Anatomy & Physiology of Bone Normal cortical bone is water, organic matter (collagen, ground substance, cellular elements) and inorganic matter (bone mineral) Normal cortical bone is water, organic matter (collagen, ground substance, cellular elements) and inorganic matter (bone mineral) Bone salt mineral (inorganic matters) is composed of calcium, phosphate, and hydroxyl, carbonate, citrate, sodium, magnesium, potassium, chloride and fluoride. Bone salt mineral (inorganic matters) is composed of calcium, phosphate, and hydroxyl, carbonate, citrate, sodium, magnesium, potassium, chloride and fluoride. Crystalline lattice structure Crystalline lattice structure hydroxyapatite hydroxyapatite Skeleton performs several functions: Skeleton performs several functions: Support Support Protection Protection Movement Movement Blood formation Blood formation

3. Anatomy & physiology of Bone Bone is metabolically active tissue with nutrients being exchanged between blood and bone. Bone is metabolically active tissue with nutrients being exchanged between blood and bone. Main difference between bone and other connective tissue is that it is calcified. Main difference between bone and other connective tissue is that it is calcified.

4. Anatomy & Physiology of Bone Skeleton has two parts: Skeleton has two parts: Axial: skull, spine and Axial: skull, spine and thoracic girdle Appendicular: upper Appendicular: upper extremities, pelvis and lower extremities

5. Gross Structure of Bone Skeletal system contains 206 bones Skeletal system contains 206 bones Tubular Bones Tubular Bones Humerus, radius, ulna, femur, tibia and fibula Humerus, radius, ulna, femur, tibia and fibula Metacarpals, metatarsals, and phalanges Metacarpals, metatarsals, and phalanges Short Bones Short Bones Wrist (carpals), ankle (tarsals), sesamoids Wrist (carpals), ankle (tarsals), sesamoids Flat Bones Flat Bones Ribs, sternum, scapulae, several skull bones Ribs, sternum, scapulae, several skull bones Irregular Bones Irregular Bones Spine, pelvis, some bones in skull Spine, pelvis, some bones in skull

6. Radiopharmaceuticals Can be analogs of calcium, hydroxyl groups, or phosphates Can be analogs of calcium, hydroxyl groups, or phosphates First 99m Tc phosphate complex for bone imaging was introduced in 1971. First 99m Tc phosphate complex for bone imaging was introduced in 1971. Most widely used: Technetium based methylene diphosphonate (MDP) Most widely used: Technetium based methylene diphosphonate (MDP) 18 F FDG with PET imaging 18 F FDG with PET imaging

7. Accumulation The mechanisms for bone accumulation of imaging agents are not completely understood. The mechanisms for bone accumulation of imaging agents are not completely understood. It is probably related to the exchange of the phosphorus groups onto the calcium of hydroxyapatite. It is probably related to the exchange of the phosphorus groups onto the calcium of hydroxyapatite. Calcium analogs or phosphate compounds have a low concentration in blood and tissue. Calcium analogs or phosphate compounds have a low concentration in blood and tissue. 99mTc phosphate will also show renal activity ~ these agents are excreted through the urinary tract. 99mTc phosphate will also show renal activity ~ these agents are excreted through the urinary tract.

8. Kit Preparation Air should not be mixed into the kit vial during preparation. This oxidation would cause poor tagging. Air should not be mixed into the kit vial during preparation. This oxidation would cause poor tagging. If injected over 4 hours after preparation, thyroid and gastric activity may be seen. If injected over 4 hours after preparation, thyroid and gastric activity may be seen.

9. Patient Preparation No prep before exam No prep before exam Following injection, they should be well hydrated to help with clearance from soft tissue. Following injection, they should be well hydrated to help with clearance from soft tissue. 4-6 glasses of liquid is adequate 4-6 glasses of liquid is adequate They should be encouraged to void frequently to reduce radiation dose to bladder. They should be encouraged to void frequently to reduce radiation dose to bladder.

10. Common Reasons for Bone Scanning Detection or follow-up of metastatic disease (breast, prostate or lung cancer) Detection or follow-up of metastatic disease (breast, prostate or lung cancer) Differentiate between osteomyelitis and cellulitis Differentiate between osteomyelitis and cellulitis Determine bone viability (infarct or avascular necrosis Determine bone viability (infarct or avascular necrosis Evaluate fractures Evaluate fractures Evaluate prosthetic joints for loosening or infection Evaluate prosthetic joints for loosening or infection Evaluate bone pain Evaluate bone pain Evaluate finding on CT or Radiograph Evaluate finding on CT or Radiograph Increased alkaline phosphatase Increased alkaline phosphatase

11. Technique Inject 10 – 25 mCi of Technetium based radiopharmaceutical (usually MDP) Inject 10 – 25 mCi of Technetium based radiopharmaceutical (usually MDP) Acquire blood flow and pool if needed Acquire blood flow and pool if needed Image 2-4 hours later Image 2-4 hours later Pt. should be well hydrated during the wait time to help with soft-tissue clearance. Pt. should be well hydrated during the wait time to help with soft-tissue clearance. Pt. should void immediately prior to imaging Pt. should void immediately prior to imaging Spot views or whole-body imaging Spot views or whole-body imaging SPECT may help improve lesion or fracture localization SPECT may help improve lesion or fracture localization

12. Three-Phase Blood Flow Blood Flow 2-4 second images for 40-60 seconds 2-4 second images for 40-60 seconds Blood Pool Blood Pool Static image obtained for 300,000-500,000 counts Static image obtained for 300,000-500,000 counts Delay Delay 2-4 hours after injection (5 + hrs. for osteomyelitis of feet) 2-4 hours after injection (5 + hrs. for osteomyelitis of feet) 300,000-500,000 count static images 300,000-500,000 count static images 100,000 counts image should be done if 4 th phase is needed 100,000 counts image should be done if 4 th phase is needed 4 th phase: acquired 24 hours later 4 th phase: acquired 24 hours later 100,000 counts to compare to previous day 100,000 counts to compare to previous day

13. SPECT Single Photon Emission Computed Tomography Pelvis, spine, TMJ, facial bones, knees Pelvis, spine, TMJ, facial bones, knees Detector to patient distance should be minimal Detector to patient distance should be minimal 30-45 minutes 30-45 minutes Single head camera 64X64 matrix Single head camera 64X64 matrix Newer cameras can use 128X128 matrix Newer cameras can use 128X128 matrix Large number of views 120 – 128 in 360 degrees Large number of views 120 – 128 in 360 degrees These parameters give very high counts and very high resolution These parameters give very high counts and very high resolution Reconstructed images include transverse, coronal and sagittal slices Reconstructed images include transverse, coronal and sagittal slices

14. Instrumentation Anger scintillation camera Anger scintillation camera High-resolution collimator High-resolution collimator Multiple, individual static images should be taken for equal amounts of time. Multiple, individual static images should be taken for equal amounts of time. Allows for comparison of image densities. Allows for comparison of image densities.

15. Normal Scan Children: areas of growth (epiphyses) show intense uptake Children: areas of growth (epiphyses) show intense uptake Adults: Adults: Increase in nasopharynx Increase in nasopharynx Skull may be patchy Skull may be patchy Maxillary or mandibular activity due to dental disease Maxillary or mandibular activity due to dental disease Increase in lower cervical spine and knees due to degenerative changes Increase in lower cervical spine and knees due to degenerative changes Anterior view: prominent sternum, sc joints, ac joints, shoulders, iliac crests and hips show increase in activity. Anterior view: prominent sternum, sc joints, ac joints, shoulders, iliac crests and hips show increase in activity. Posterior view: thoracic spine, si joints and tips of scapulae are prominent Posterior view: thoracic spine, si joints and tips of scapulae are prominent Any asymmetric activity is suspicious Any asymmetric activity is suspicious

17. Causes for Increased Activity Primary bone tumor Primary bone tumor Metastatic Disease Metastatic Disease Osteomyelitis Osteomyelitis Trauma (fracture, postsurgical) Trauma (fracture, postsurgical) Loose prosthesis Loose prosthesis Degenerative or arthritic changes Degenerative or arthritic changes Osteoid osteoma Osteoid osteoma Paget’s Disease Paget’s Disease

18. Generalized increased bone activity Superscan Superscan (no renal activity seen) Hyperparathyroidism Hyperparathyroidism Renal osteodystrophy Renal osteodystrophy Diffuse metastases Diffuse metastases Hematologic disorders Hematologic disorders

19. Poor scan Decreased cardiac output Decreased cardiac output Renal failure Renal failure Extravasation of radiopharmaceutical during injection Extravasation of radiopharmaceutical during injection Kit breakdown Kit breakdown

20. Metastatic Disease 30-50% of patients with metastases do not have pain 30-50% of patients with metastases do not have pain Tumors that are more likely to spread to bone: breast, lung and prostate Tumors that are more likely to spread to bone: breast, lung and prostate Tumors with low rates of bone metastases: colon, cervix, uterus, head and neck Tumors with low rates of bone metastases: colon, cervix, uterus, head and neck Most metastases are seen in multiple areas. (exception is single sternal lesion in breast cancer pt.) Most metastases are seen in multiple areas. (exception is single sternal lesion in breast cancer pt.) PSA (prostate-specific antigen): less than 10-15 ng/mL = likelyhood of positive bone scan with metastases is low. PSA (prostate-specific antigen): less than 10-15 ng/mL = likelyhood of positive bone scan with metastases is low. Cold lesions: extremely aggressive tumor, decreased blood supply, or significant marrow involvement. Cold lesions: extremely aggressive tumor, decreased blood supply, or significant marrow involvement.

22. Osteogenic Sarcoma Osteosarcoma is a Osteosarcoma is a bone-forming lesion Appearance varies Appearance varies widely depending on the vascularity and aggressiveness of the tumor. Increased activity is usually intense and often patchy with photopenic areas. Increased activity is usually intense and often patchy with photopenic areas.

23. Ewing’s Sarcoma Relatively common bone tumor Relatively common bone tumor Occurs mostly in pelvis or femur Occurs mostly in pelvis or femur Activity is intense and homogeneous. Activity is intense and homogeneous. Tumor is very vascular Tumor is very vascular 40-50% of patient’s with Ewing’s sarcoma or osteosarcoma develop metastases within 2 years. Follow-up bone scans are recommended. 40-50% of patient’s with Ewing’s sarcoma or osteosarcoma develop metastases within 2 years. Follow-up bone scans are recommended.

24. Trauma Bone scan appearance of Fractures: Bone scan appearance of Fractures: Acute: 3-4 weeks~generalized diffuse increase around fracture site Acute: 3-4 weeks~generalized diffuse increase around fracture site Subacute: 2-3 months~activity more localized and intense Subacute: 2-3 months~activity more localized and intense Healing phase: longer period ~gradual decline in intensity Healing phase: longer period ~gradual decline in intensity Early increase in activity is a result of hyperemia and inflammation. Early increase in activity is a result of hyperemia and inflammation. Repair begins within a few hours and reaches maximum in 2-3 weeks. Repair begins within a few hours and reaches maximum in 2-3 weeks. Age: has been found to be a minor variable. However, about 3 days are needed to detect occult hip fracture in elderly patients. Age: has been found to be a minor variable. However, about 3 days are needed to detect occult hip fracture in elderly patients.

25. Avascular Necrosis Involving the hip Involving the hip Usually due to trauma Usually due to trauma Decrease in blood flow and Decrease in blood flow and blood pool Decreased activity on Decreased activity on delay images MRI can also be done for this MRI can also be done for this

26. Stress Fractures Not visualized for 7 to 10 days on radiograph. Not visualized for 7 to 10 days on radiograph. Can be seen on a radionuclide bone scan about 24 hrs. after onset of pain. Can be seen on a radionuclide bone scan about 24 hrs. after onset of pain. Stress fractures: increased blood flow and pool~delay tends to image as a focal hot spot. Stress fractures: increased blood flow and pool~delay tends to image as a focal hot spot. Shin splints: normal blood flow and blood pool~delay shows linear increased activity along posteromedial tibial cortex. Shin splints: normal blood flow and blood pool~delay shows linear increased activity along posteromedial tibial cortex.

28. Child Abuse Rib and thoracic spine fractures are a strong indication of physical abuse. Rib and thoracic spine fractures are a strong indication of physical abuse.

29. Osteomyelitis, Cellulitis & Septic Arthritis Radiopharmaceuticals: Radiopharmaceuticals: 99m Tc –diphosphonate 67 Ga citrate 111 In labeled leukocytes 99m Tc labeled leukocytes Cellulitis: increased blood flow and blood pool, no focal area of increase on delay. Cellulitis: increased blood flow and blood pool, no focal area of increase on delay. Osteomyelitis: increased blood flow and blood pool, with focal increased area on delay. Usually only on one side of a joint. Osteomyelitis: increased blood flow and blood pool, with focal increased area on delay. Usually only on one side of a joint. Septic Arthritis: increased activity in all three phases. Involved both sides of the joint. Septic Arthritis: increased activity in all three phases. Involved both sides of the joint.

30. Paget’s Disease Intense increase in activity due to increased regional blood flow. Intense increase in activity due to increased regional blood flow. Usually conforms to the shape of the involved bone. Usually conforms to the shape of the involved bone. Notable expansion or Notable expansion or enlargement of the bone.

31. Reflex Sympathetic Dystrophy (RSD) Usually prior trauma, myocardial infarction, or neurologic abnormality. Usually prior trauma, myocardial infarction, or neurologic abnormality. Increased blood flow and Increased blood flow and blood pool to affected limb, increased asymmetric periarticular activity around all joints of hand or foot.

32. Bone Marrow Imaging Radiopharmaceutical: 99mTc sulfur colloid Radiopharmaceutical: 99mTc sulfur colloid Localizes in marrow because the particles are phagocytized by RES cells in the marrow. Localizes in marrow because the particles are phagocytized by RES cells in the marrow. Intense liver and spleen activity must be covered with a lead shield. Intense liver and spleen activity must be covered with a lead shield. MRI usually done MRI usually done

33. Joint Imaging Evaluate inflammatory joint disease Evaluate inflammatory joint disease Radiopharmaceuticals: Radiopharmaceuticals: 99m Tc pertechnetate 99m Tc pertechnetate 99m Tc phosphate compounds (most sensitive for knee or sacroiliac inflammatory disease) 99m Tc phosphate compounds (most sensitive for knee or sacroiliac inflammatory disease) Can detect disease before radiographs Can detect disease before radiographs

34. Therapy of Painful Bone Metastases Lesions that are unresponsive to radiotherapy or chemotherapy. Lesions that are unresponsive to radiotherapy or chemotherapy. Usually men with prostate cancer Usually men with prostate cancer For pain management (not a cure) For pain management (not a cure) Increase in pain 2-3 days after treatment and can last several days. Increase in pain 2-3 days after treatment and can last several days. Pain improvement starts at 7-20 days after treatment and can last 3-6 months. Pain improvement starts at 7-20 days after treatment and can last 3-6 months. Routine bone scan is done first to ensure there will be bone uptake. Routine bone scan is done first to ensure there will be bone uptake.

35. Therapy of Painful Bone Metastases Radiopharmaceutical: Strontium-89 chloride (Metastron) Radiopharmaceutical: Strontium-89 chloride (Metastron) Decays by beta-emission Decays by beta-emission Half-life 50.6 days Half-life 50.6 days Depresses the bone marrow and should not be used if leukocyte or platelet count is low. Depresses the bone marrow and should not be used if leukocyte or platelet count is low. Typical dose is 40-60 uCi / kg : up to 4mCi Typical dose is 40-60 uCi / kg : up to 4mCi Slow 1-2 minute injection using plastic shielding Slow 1-2 minute injection using plastic shielding Should not be given to patients with life expectancy less than 3 months. Patients cannot be cremated in many states. Should not be given to patients with life expectancy less than 3 months. Patients cannot be cremated in many states. Cost : $3000 + (cost effective compared to radiation therapy, chemotherapy, and analgesic pain medication Cost : $3000 + (cost effective compared to radiation therapy, chemotherapy, and analgesic pain medication

36. Therapy of Painful Bone Metastases Other Radiopharmaceuticals: Other Radiopharmaceuticals: Rhenium-186 HEDP ~not approved in the U.S., but widely used in Europe Rhenium-186 HEDP ~not approved in the U.S., but widely used in Europe Samarium-153 EDPMT (Quadramet) Samarium-153 EDPMT (Quadramet) Short half-life of 46 hours Short half-life of 46 hours In addition to beta emission, also has a gamma emission that can be imaged In addition to beta emission, also has a gamma emission that can be imaged Usually scanned 6 hrs after administered Usually scanned 6 hrs after administered