**3. Applications of skeletal radionuclide imaging**

 It is definite that the skeletal radionuclide imaging can present the information of blood flow and osteogenesis of regional area once. There are various abnormalities in skeletal radionuclide imaging, whatever the defects or increased uptake of radionuclide; they can manifest some clue of the lesions. We conclude some abnormal results as below, and describe the details as follow based on the clinical applications.

concomitant drug therapy should be suspected. Here shows a normal skeleton scintigram

Fig. 1. Normal skeletal scintigram shows the symmetric and uniform activity absorption in

A number of normal variants must be recognized for correct interpretation. Here we list

②The anterior aspect of the mandible may appear as a "hot spot" on lateral views of the

③The laryngotracheal cartilages are usually seen in adults probably related to some degree

④The thyroid gland can be visualized because of avid accumulation of unbound

⑤Some mild diffuse asymmetry in paired joints is commonly seen in adults especially in

⑥Some asymmetry is frequently seen in the sacroiliac joints, and this should be interpreted

 It is definite that the skeletal radionuclide imaging can present the information of blood flow and osteogenesis of regional area once. There are various abnormalities in skeletal radionuclide imaging, whatever the defects or increased uptake of radionuclide; they can manifest some clue of the lesions. We conclude some abnormal results as below, and

①Bilaterally increased radionuclide concentration may be normal.

(Figure 1).

anterior and posterior image.

skull.

of calcification.

pertechnetate.

some possible conditions as below.

shoulders and correlates with handedness.

**3. Applications of skeletal radionuclide imaging** 

describe the details as follow based on the clinical applications.

with caution in patients with scoliosis.

①Asymmetric focal areas of increased or decreased activity: basically, this type of abnormality can happen in almost every scintigram. Focal increased activity can be associated with more blood flow (caused by hyperaemia, such as trauma, inflammation, etc) and active of osteogenesis (such as bone metastases of prostate cancer).

②"Super scan" is another scintigraphic pattern, with good bone-to-soft tissue background ratio, bone uptake showing brightly, absent or faint visualization of kidney and bladder, an increased uptake in the axial versus appendicular skeleton (appendicular skeleton, distal extremities, facial bones, subtle asymmetries of the rib, skull vault, and proximal long bones, and no soft-tissue uptake apparent at normal intensities). In some patients with breast cancer or prostate cancer the entire axial skeleton becomes diffusely and rather uniformly involved with metastatic disease (Figure 2).

Fig. 2. A patient diagnosed as prostate cancer, the whole body bone scan with 99mTc-MDP showed "super scan": absent visualization of kidney, increased uptake in the axial versus appendicular skeleton and no soft-tissue uptake apparent at normal intensities.

③Cold areas, which means diminished activity or none distribution of activity, is indicative of osteonecrosis, osteoporosis, osteomalacia, multiple myeloma, radiation or steroid therapy, end-stage cancer patients with diminished metabolism, renal cell carcinoma, thyroid cancer, anaplastic tumors, neuroblastoma.

④"Donut" sign is the typical scintigram of osteonecrosis of the femoral head. The cold area within the femoral head is highly specific and is the earliest scintigraphic evidence of avascular necrosis. Over a period of weeks to months, increased uptake represents revascularization and repair surrounds, and eventually replaces the region of photopenia. The central region of photopenia with surrounding zone of increased uptake is termed as "donut" sign (Figure 3).

Skeleton System 295

The most common clinical application of skeletal imaging is in evaluating patients with extraskeletal primary malignancies for the presence of metastatic disease and staging metastatic disease. In many patients the presence of extent of skeletal metastasis directly influences treatment decisions and prognosis. Bone imaging plays an important role in treatment of bone pain and pathological fracture which are common management problems

Anterior and posterior images of the whole body scan are generally obtained. Metastases to bone are common in several primary malignancies, including lung, breast, and prostate carcinomas (Figure 5-6). Metastases to the spine are difficult to detect radiographically, since loss of approximately 50% of the mineral content of the bone must occur before lytic lesions are detected. The usual scintigraphic pattern of skeletal metastatic disease is multiple focal lesions throughout the skeleton, with the greatest involvement generally in the axial skeleton. The area of abnormal radiopharmaceutical deposition represents the edge of the

As metastatic lesions grow in the marrow space, the surrounding bone remodels through osteoclastic (resorptive) and osteoblastic (depositional) activity. The relative degrees of bone resorption and deposition elicited are highly variable among the different types of tumors and sometimes even different locations for the same tumor. The relationship between the two remodelling processes determines whether a metastatic deposit will appear as

predominantly lytic or sclerotic or will exhibit a mixed pattern radiographically.

Fig. 5. The image showed multiple hot spot in skull, vertebrae, ribs, pelvis, femur, etc. Combined with the history of prostate cancer and night bone pain, it was concluded as bone

**3.1 Metastatic diseases** 

metastases of prostate cancer.

in patients with skeletal metastatic disease.

metastatic deposit where osteoblastic repair is attempted.

Fig. 3. The image showed "donut" sign in bilateral femoral head (worse in left side than right side), which is the diagnostic evidence of femoral head necrosis resulting from longtime use of dexamethasone.

⑤No uptake in focal areas: patients receive radiation therapy, bone infarct, avascular necrosis, metal prosthesis, bone infiltrated by tumor, poor venous return, edema in extremity may seen cold spot in focal area.

⑥Three phase bone imaging: it is one of the types of imaging protocols, and can help the qualitative diagnosis of some skeletal diseases, such as increased uptake in flow, blood pool, and delays in osteomyelitis cases; increased uptake in flow and blood-pool with mild or no uptake in delays in cellutitis; increased activity in and around joints in flow, blood pool, and delays in arthritis; increased vascular flow, blood pool, and delays focally in primary malignant tumor (Figure 4); increased blood pool and delays, focally intense in benign primary tumor.

Fig. 4. Three phase bone imaging showed increased activity in left distal femur in blood flow phase (A), blood pool phase (C), and delayed phase (D). Malignant bone tumor: blood supply obviously increased in blood flow phase, vascular extension can be seen. Irregular tracer accumulated in soft tissue, in blood pool phase. Hot spot accumulation can be found on bone in delayed phase. In this case the patient was diagnosed as left femur osteogenic sarcoma by pathological proven finally.

Fig. 3. The image showed "donut" sign in bilateral femoral head (worse in left side than right side), which is the diagnostic evidence of femoral head necrosis resulting from long-

⑤No uptake in focal areas: patients receive radiation therapy, bone infarct, avascular necrosis, metal prosthesis, bone infiltrated by tumor, poor venous return, edema in

⑥Three phase bone imaging: it is one of the types of imaging protocols, and can help the qualitative diagnosis of some skeletal diseases, such as increased uptake in flow, blood pool, and delays in osteomyelitis cases; increased uptake in flow and blood-pool with mild or no uptake in delays in cellutitis; increased activity in and around joints in flow, blood pool, and delays in arthritis; increased vascular flow, blood pool, and delays focally in primary malignant tumor (Figure 4); increased blood pool and delays, focally intense in benign

Fig. 4. Three phase bone imaging showed increased activity in left distal femur in blood flow phase (A), blood pool phase (C), and delayed phase (D). Malignant bone tumor: blood supply obviously increased in blood flow phase, vascular extension can be seen. Irregular tracer accumulated in soft tissue, in blood pool phase. Hot spot accumulation can be found on bone in delayed phase. In this case the patient was diagnosed as left femur osteogenic

time use of dexamethasone.

primary tumor.

extremity may seen cold spot in focal area.

sarcoma by pathological proven finally.

### **3.1 Metastatic diseases**

The most common clinical application of skeletal imaging is in evaluating patients with extraskeletal primary malignancies for the presence of metastatic disease and staging metastatic disease. In many patients the presence of extent of skeletal metastasis directly influences treatment decisions and prognosis. Bone imaging plays an important role in treatment of bone pain and pathological fracture which are common management problems in patients with skeletal metastatic disease.

Anterior and posterior images of the whole body scan are generally obtained. Metastases to bone are common in several primary malignancies, including lung, breast, and prostate carcinomas (Figure 5-6). Metastases to the spine are difficult to detect radiographically, since loss of approximately 50% of the mineral content of the bone must occur before lytic lesions are detected. The usual scintigraphic pattern of skeletal metastatic disease is multiple focal lesions throughout the skeleton, with the greatest involvement generally in the axial skeleton. The area of abnormal radiopharmaceutical deposition represents the edge of the metastatic deposit where osteoblastic repair is attempted.

As metastatic lesions grow in the marrow space, the surrounding bone remodels through osteoclastic (resorptive) and osteoblastic (depositional) activity. The relative degrees of bone resorption and deposition elicited are highly variable among the different types of tumors and sometimes even different locations for the same tumor. The relationship between the two remodelling processes determines whether a metastatic deposit will appear as predominantly lytic or sclerotic or will exhibit a mixed pattern radiographically.

Fig. 5. The image showed multiple hot spot in skull, vertebrae, ribs, pelvis, femur, etc. Combined with the history of prostate cancer and night bone pain, it was concluded as bone metastases of prostate cancer.

Skeleton System 297

Fig. 7. Anterior and posterior whole body scintigram of a patient with osteosarcoma in the left distal femur. The degree of tracer accumulation in the lesion is striking. Note also the "watershed" phenomenon with increased tracer accumulation in all of the bones of the left lower extremity above and below the lesion. The increased blood flow induced by the

Another primary malignant disease commonly involving bone is multiple myeloma (MM). MM is really a disease of the red marrow space, and the most frequently involved skeletal structures are the vertebrae, pelvis, ribs, and skull (Figure 8). On skeletal scintigram the only finding in MM may be osteopenia. Unless an associated fracture or a focal lesion such as a plasmacytoma is present, skeletal scintigrams are often normal. MRI is an excellent modality

osteosarcoma results in increased tracer delivery to the entire limb.

for evaluating the marrow space for areas of involvement.

Fig. 6. The image showed multiple focal lesions in bone of patient with breast cancer.

False negative scans have been related to several factors. If the skeleton is diffusely involved with metastatic disease, the focal nature of the lesions might not be apparent. Metastatic lesions may have no associated osteoblastic activity and thus may not be detected by bone scan or may be detected as a photon-deficient area.

### **3.2 Primary malignant bone tumors**

Bone scanning is also used for the evaluation of primary bone neoplasm. Usually the patient has already had radiographs of the primary tumor, but the bone scan offers additional information of that area. The extent of the abnormality on the bone scan is generally not much different from the radiographically apparent lesion. The value of bone scanning in patients with primary bone malignancy lies in the detection of the disease elsewhere.

Uptake of bone-seeking radiopharmaceuticals in primary bone tumors is avid and frequently striking. PET imaging with FDG is being explored for primary bone tumors. FDG uptake correlates with tumor metabolism. Scans can be helpful in localizing sites for biopsy and in assessing response to preoperative radiation and chemotherapy.

99mTc-MIBI have been used for sarcoma imaging to determine whether tumors are low or high grade and to assess response to therapy. As with FDG, high-grade tumors show higher uptake. Successful radiation therapy or chemotherapy is associated with decreasing uptake. Studies of primary tumor have led to at least one important observation about skeletal tracer uptake. Many tumors elicit marked hyperemia. The increased blood flow is not restricted to the tumor itself but affects the entire watershed distribution of regional flow, most characteristically involving an entire extremity (Figure 7).

Fig. 6. The image showed multiple focal lesions in bone of patient with breast cancer.

scan or may be detected as a photon-deficient area.

**3.2 Primary malignant bone tumors** 

False negative scans have been related to several factors. If the skeleton is diffusely involved with metastatic disease, the focal nature of the lesions might not be apparent. Metastatic lesions may have no associated osteoblastic activity and thus may not be detected by bone

Bone scanning is also used for the evaluation of primary bone neoplasm. Usually the patient has already had radiographs of the primary tumor, but the bone scan offers additional information of that area. The extent of the abnormality on the bone scan is generally not much different from the radiographically apparent lesion. The value of bone scanning in

Uptake of bone-seeking radiopharmaceuticals in primary bone tumors is avid and frequently striking. PET imaging with FDG is being explored for primary bone tumors. FDG uptake correlates with tumor metabolism. Scans can be helpful in localizing sites for biopsy

99mTc-MIBI have been used for sarcoma imaging to determine whether tumors are low or high grade and to assess response to therapy. As with FDG, high-grade tumors show higher uptake. Successful radiation therapy or chemotherapy is associated with decreasing uptake. Studies of primary tumor have led to at least one important observation about skeletal tracer uptake. Many tumors elicit marked hyperemia. The increased blood flow is not restricted to the tumor itself but affects the entire watershed distribution of regional flow, most

patients with primary bone malignancy lies in the detection of the disease elsewhere.

and in assessing response to preoperative radiation and chemotherapy.

characteristically involving an entire extremity (Figure 7).

Fig. 7. Anterior and posterior whole body scintigram of a patient with osteosarcoma in the left distal femur. The degree of tracer accumulation in the lesion is striking. Note also the "watershed" phenomenon with increased tracer accumulation in all of the bones of the left lower extremity above and below the lesion. The increased blood flow induced by the osteosarcoma results in increased tracer delivery to the entire limb.

Another primary malignant disease commonly involving bone is multiple myeloma (MM). MM is really a disease of the red marrow space, and the most frequently involved skeletal structures are the vertebrae, pelvis, ribs, and skull (Figure 8). On skeletal scintigram the only finding in MM may be osteopenia. Unless an associated fracture or a focal lesion such as a plasmacytoma is present, skeletal scintigrams are often normal. MRI is an excellent modality for evaluating the marrow space for areas of involvement.

Skeleton System 299

Skeletal trauma is common and presents both an opportunity and a problem in skeletal scintigraphy. As we known, the first choice for suspected bone fracture is radiography, which shows the fracture line and type clearly. But SPECT bone imaging has its own advantages in some aspects. SPECT is a useful adjunct in the course of process such as stress fracture. Normal bone is constantly remodelling, bone resorption and deposition are balanced. When the skeleton is placed under stress the rate of remodelling increases, and

The time a fracture takes to return to normal scintigraphically depends primarily on its

Fig. 10. Occult fracture of the left foot 4th toe, which can not be detected by radiography.

In addition to being used in the evaluation of malignant disease involving the skeleton, radionuclide bone imaging is helpful in the assessment of several other non-malignant processes, such as patients with suspected osteomyelitis and diskitis. Acute hematogenous osteomyelitis typically begins by seeding of the infectious organism in the marrow space. A three-phase bone scan is performed by acquiring a rapid blood flow sequence of images over the interested area during agent injection. Early images (blood flow phase) are important in evaluating inflammatory processes. Flow images are performed 40 to 60sec and 2 to 4 sec for each frame. Blood pool images are then immediately obtained for totally 300 to 500 kcounts without moving the patient, and delayed images are taken as necessary. Both osteomyelitis and cellutitis can cause early increased radioactivity accumulation due to an increased vascular response to the affected area. The third phase is routine scanning at 2 to 3 hr after injection. Sometimes there will be a forth phase that can be added 24hr delay. Osteomyelitis demonstrates focally increased activity in the involved bone on both the blood-pool and routine images (Figure 11). Since the use of bone imaging for detecting osteomyelitis, it has been found that several patients do not subsequently develop the typical radiographic changes because the early treatment prevents the development of

**3.4 Trauma and athletic injuries** 

**3.5 Osteomyelitis** 

radiographic abnormalities.

that will result in change of activity in bone scintigraphy,

location and the degree of damage to the skeleton.

Fig. 8. Multiple myeloma, showed multiple focal accumulation of radioactivity in bone.
