**Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice**

Jing jing Peng

*Dept. Beijing Institute of Traumatology and Orthopaedics Beijing Ji Shui-Tan Hospital The 4th Clinical Hospital of Peking University China* 

## **1. Introduction**

16 Will-be-set-by-IN-TECH

68 Soft Tissue Tumors

Mutlu, H., Silit, E., Pekkafali, Z., Basekim, C., Ozturk, E., Sildiroglu, O., Kizilkaya, E. & Karsli,

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malignant lesions, *Clinical Imaging* 30(1): 37–42.

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*Clin N Am* 3: 669–694.

approach, *Data Mining and Knowledge Discovery* 1: 317–327.

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*of Computer Vision and Applications, Vol.2, Signal Processing and Pattern Recognition*,

Soft tissue is defined as the supportive tissue of various organs,the term soft tissue tumors defines neoplasms derived from soft tissue. At the clinical level, a mass is the most common sign of a soft tissue tumor. However, the clinical manifestations and signs of parathyroid adenoma are not in the neck at first since, very often, there are patients who's neck is normal at primary physical examination. Bone pain or dysfunction fractures are the main reason for the parathyroid tumor patients to visit the hospital. Parathyroid tumor (Figure 1) is an endocrine tumor, mainly associated with bone metabolism therefore the patients go to the orthopedic department first. Although the parathyroid tumor is benign if patients do not get timely and accurate diagnosis and effective treatment(surgical removal of parathyroid adenoma), they will not only receive the delayed treatment but also, a significant decline of life quality will occur. The loss of ability to work increases the burden on families and society.

#### Fig. 1. Parathyroid adenoma

The neck SPECT/CT scan function-anatomy fused Imaging reveals A focus of increased 99mTc-MIBI activity at the posterior inferior of the right lobe of the thyroid which consistent with parathyroid adenoma

Effective treatment for parathyroid tumors depends on timely, accurate diagnosis.Doctor Peng Jing Jing, <Advancement in the Application of Nuclear Medicine> published in

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 71

Mrs. Liang was admitted into hospital on 1998.12.07 her X-Ray showed the Femoral neck

On questioning her, I found that Mrs. liang had been C/O leg pain for 3 years, Also she felt

On examination, I found her right leg was external rotated and shorten, there was tenderness in the hip joint and mildly swollen. Her Vital signs were normal (Temp\ pulse

Bone scan(99mTc-MDP)patterns in advanced metabolic bone disease (please see attached

99mTc-MDP Bone scan showed metabolic disease

Fig. 3. Diagnostic Imaging of hyperparathyroidism resulted in metabolic bone disease

Beijing JST hospital 31st Xin Jie-kou East Street, Beijing, P.R. China

Dear Dr. Sun: 1999.01.11 RE: Mis. Liang beauty DOB1958.07.09 Age: 40 ID: 305447 SPECT: 981193 Address: Hebei China ——————————————————————

She was C/O painful hip radiating to her legs.

severe right hip pain before my seeing her 2 /52.

Serum Ca (calcium), P (phosphorus), AKP, PTH, ESR

 Serum Ca was high 3.11(2.25-2.75) mmol/L, Serum P was lower 0.85(0.97-1.6) mmol/L.

AKP was high 502(25-90) IU/L. PTH (parathyroid hormone) was high.

BMD was low: T scores of < 2.5SD

characteristic abnormalities.

Hip X-ray BMD (bone mineral density) ECT: bone scan and parathyroid tumor image

\Resp \B/P).

Ultra scan Blood tests:

picture):

Tests carried out were:

I saw this pleasant lady in my inpatients clinic on 1998.12 .09

pathological fracture of the right femur. ? metastatic bone disease.

The results showed she had a hypercalcemia and hypophosphatemia:

Hip X-ray showed: The intertrochanter's fracture of the right femur.

Apr.2001 V7N4:59-61 Journal of "China Contemporary Medicine", reported the use of nuclear medicine, that is molecular imaging, which enables early diagnosis and successful treatment of patients with parathyroid adenoma. The cases in clinical with SPECT for 99mTc-MDP whole body bone scan and 99mTc-MIBI parathyroid tumor imaging, in which patients receive timely diagnosis and successful treatment, recover and live a happy life[3]. In recent years, as the clinic study of new technology and equipment in bone-joint disorders, orthopedic clinical applications of molecular imaging and promotion of the Chinese doctors for parathyroid tumor diagnosis and treatment, medical science has made a positive contribution [4].

Fig. 2. A 39 years-old woman complained of painful bone and joint for a long time with occurred fracture time and again. 99mTc-MDP Bone Scan shows: metabolic bone disease which causes the patient disabled. Her diagnosis is Parathyroid adenoma and she was performed a parathyroid adenoma ectomy in surgical operation.

The contribution showed typical diagnostic -Imaging of hyperparathyroidism- resulted in metabolic bone disease characteristic abnormalities (Figure.3):


There are two main features of metabolic bone disease due to hyperparathyroidism in 99mTc-MDP bone imaging: (1) Increased uptake in calvaria and jawbone showed "the Black skull". (2) Bone scan is clear showed total body as "Super Scan": Generalized increased uptake with increased contrast between bone and soft tissue: increased uptake in long bones and increased uptake in axial skeleton, increased uptake in periarticular areas, increased uptake in costochondral junctions (beads) and increased uptake in sternum (tie sternum).The patient right leg was shorten with foci of increased uptake due to dysfunction fracture, brown tumor due to fibrocystic changes.

Apr.2001 V7N4:59-61 Journal of "China Contemporary Medicine", reported the use of nuclear medicine, that is molecular imaging, which enables early diagnosis and successful treatment of patients with parathyroid adenoma. The cases in clinical with SPECT for 99mTc-MDP whole body bone scan and 99mTc-MIBI parathyroid tumor imaging, in which patients receive timely diagnosis and successful treatment, recover and live a happy life[3]. In recent years, as the clinic study of new technology and equipment in bone-joint disorders, orthopedic clinical applications of molecular imaging and promotion of the Chinese doctors for parathyroid tumor diagnosis and treatment, medical science has made a positive

Fig. 2. A 39 years-old woman complained of painful bone and joint for a long time with occurred fracture time and again. 99mTc-MDP Bone Scan shows: metabolic bone disease which causes the patient disabled. Her diagnosis is Parathyroid adenoma and she was

The contribution showed typical diagnostic -Imaging of hyperparathyroidism- resulted in

2. Generalized increased uptake with increased contrast between bone and soft tissue due

6. Whole body Bone scan patterns in advanced metabolic bone disease and insufficiency

There are two main features of metabolic bone disease due to hyperparathyroidism in 99mTc-MDP bone imaging: (1) Increased uptake in calvaria and jawbone showed "the Black skull". (2) Bone scan is clear showed total body as "Super Scan": Generalized increased uptake with increased contrast between bone and soft tissue: increased uptake in long bones and increased uptake in axial skeleton, increased uptake in periarticular areas, increased uptake in costochondral junctions (beads) and increased uptake in sternum (tie sternum).The patient right leg was shorten with foci of increased uptake due to dysfunction fracture,

performed a parathyroid adenoma ectomy in surgical operation.

metabolic bone disease characteristic abnormalities (Figure.3): 1. The Black skull: increased uptake in calvaria and jawbone.

to bone turnover speed and subtracted kidney image.

4. Foci of increased uptake due to fracture or brown tumor in rib cage. 5. Decreased uptake brown tumor in the right ilium as doughnut .

3. Tie sternum and Cage beads.

fracture in right neck of femur.

brown tumor due to fibrocystic changes.

contribution [4].

 Beijing JST hospital 31st Xin Jie-kou East Street, Beijing, P.R. China Dear Dr. Sun: 1999.01.11 RE: Mis. Liang beauty DOB1958.07.09 Age: 40 ID: 305447 SPECT: 981193 Address: Hebei China —————————————————————— I saw this pleasant lady in my inpatients clinic on 1998.12 .09 She was C/O painful hip radiating to her legs. Mrs. Liang was admitted into hospital on 1998.12.07 her X-Ray showed the Femoral neck pathological fracture of the right femur. ? metastatic bone disease. On questioning her, I found that Mrs. liang had been C/O leg pain for 3 years, Also she felt severe right hip pain before my seeing her 2 /52. On examination, I found her right leg was external rotated and shorten, there was tenderness in the hip joint and mildly swollen. Her Vital signs were normal (Temp\ pulse \Resp \B/P). Tests carried out were: Hip X-ray BMD (bone mineral density) ECT: bone scan and parathyroid tumor image Ultra scan Blood tests: Serum Ca (calcium), P (phosphorus), AKP, PTH, ESR The results showed she had a hypercalcemia and hypophosphatemia: Serum Ca was high 3.11(2.25-2.75) mmol/L, Serum P was lower 0.85(0.97-1.6) mmol/L. AKP was high 502(25-90) IU/L. PTH (parathyroid hormone) was high. Hip X-ray showed: The intertrochanter's fracture of the right femur. BMD was low: T scores of < 2.5SD Bone scan(99mTc-MDP)patterns in advanced metabolic bone disease (please see attached picture): 99mTc-MDP Bone scan showed metabolic disease

Fig. 3. Diagnostic Imaging of hyperparathyroidism resulted in metabolic bone disease characteristic abnormalities.

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 73

99mTc-MDP showed "the Black skull". 99mTc- MIBI parathyroid tumor imaging not only can observe the shape and location, but also display hyper-functional status for

Achiever said: Primary hyperparathyroidism is rare in clinic. Because of occult onset and symptoms varied, misdiagnosis is made sometimes. A clear diagnosis of hyperparathyroidism and parathyroid tumors localization is the key for successful treatment. 99mTc-MDP bone scintigraphy and 99mTc -MIBI parathyroid tumor imaging has certain advantages. To be used clinically, those principal achieves can reduce misdiagnosis of primary hyperparathyroidism.

Primary hyperparathyroidism incidence rate is about 27/100000 per year, of which 80% is parathyroid tumor, 20% is benign hyperplasia, and parathyroid carcinoma is extremely rare. Because of the parathyroid hormone (PTH) secretes more than the level required to maintain normal serum calcium concentration bring about, laboratory parameters abnormal shows hypercalcemia, hypophosphatemia, elevated alkaline phosphatase and parathyroid

3. Groans--digestive symptoms: abdominal discomfort, nausea, vomiting, dyspepsia and

Early parathyroid adenoma causing bone metabolism changes in 99mTc-MDP whole body bone scan image is generalized increased uptake with characterized by the "black skull" and very clearly as "super scan" which give expression to increased contrast between bone and

Differential point in whole body bone scan image between "super scan" of HPT metabolic bone disease and wide range of bone metastasis is: HPT metabolic bone disease "super scan" is general uniformity high uptake in the axial skeleton and limb bones (Figure 5); and features of bone metastasis "super scan" are: high uptake of the mainly axial skeleton (Figure

The Patient with proceeding of parathyroid tumors, X-ray radiograph shows bone resorption caused by osteoclast, and lacy cortical thinning leading to subperiosteal bone

Radiology images can also show brown tumor formed by micro-fracture bleeding, local accumulation of macrophages, and replacement of fibrous tissue. Brown tumor and fractures in the whole body bone scan images showed localized uptake. Large fibrocystic changes (brown tumor) can be expressed as a radioactive defect of the "cold zone" (Figure 2,

1. Bones-- musculoskeletal symptoms: bone pain, dysfunction fractures; 2. Stones--symptoms of urinary system: history of kidney stones with pain;

"Super scan" of hyperparathyroidism (HPT) metabolic bone disease

soft tissue due to bone turnover speed and active bone metabolism. Metabolic bone disease with HPTdifferent from metastasis imaging

the anteposition imaging shows: brown tumor in right ilium).

4. Moans—neuropsychiatric symptoms: memory loss, depression, depressed.

6) and proximal limb bone, with point like lesions of radioactive concentration.

resorption, typical in middle phalanx radial side of index finger and middle finger.

parathyroid tumor.

**2.1 Definition** 

hormone increased.

constipation;

**2. Clinical features of parathyroid adenoma** 

Clinical symptoms mainly in four systems

Diagnostic whole body bone scan image

**2.2 Fracture and brown tumor** 

The right leg was dysfunction fracture of the right femur. In conclusion**,** I think that diagnosis is hyperparathyroidism.

So, I have had 99mTc-MIBI parathyroid tumor double-phase imaging. 99mTc-MIBI parathyroid tumor imaging not only can observe the shape and location, but can also display functional status for parathyroid tumor.

Fig. 4. 99mTc-MIBI parathyroid tumor (double-phase) imaging.

Immediate (upper) and Delayed (lower) 99mTc-MIBI imaging reveals a focus of increased activity at the inferior tip of the right lobe of the thyroid, Consistent with parathyroid adenoma.

99mTc-MIBI scan showed: right lower parathyroid adenoma (Please see attached).

Ultra scan also showed: Parathyroid tumor

Diagnosis:Primary hyperparathyroidism caused by a parathyroid adenoma

Metabolic bone disease Osteoporosis

Dysfunction fracture (the right femur).

Mrs. Liang was given operating treatments on 1998.12.21:

First, was performed parathyroid adenoma' ectomy in surgical operating theatre.

Then, Reduction of fracture and internal fixation was performed by orthopedic doctor.

Finally, the diagnosis in pathology (98-X1095) was:

Parathyroid adenoma

Focus which lead to fracture of the right femur was brown tumor

She was discharged on 1999.01.11.

She was given diet and some medication advice to help her to gain full recovery.

JST' doctor Peng Jing Jing etc. Primary Academic contributions to this project

< Application of Radionuclide Imaging in Diagnosis of hyperfunctioning Parathyroid tumors>journal of Chinese Nuclear Medicine Dec.2003[2] .Cited by Zhuhai City, Guangdong Province People's Hospital Chen Jiang lin etc. in Anthology of Medicine Apr.2006[5], the paper reported a case Qualitative and locational diagnosis with nuclear medicine of primary hyperparathyroidism and successful surgery of parathyroid adenoma: Peng Jingjing et al thought, there are two main features of metabolic bone disease due to hyperparathyroidism in 99mTc-MDP bone imaging: (1) Bone scan is clear showed total body as "Super Scan"; (2) Increased uptake in calvaria and jawbone for 99mTc-MDP showed "the Black skull". 99mTc- MIBI parathyroid tumor imaging not only can observe the shape and location, but also display hyper-functional status for parathyroid tumor.

Achiever said: Primary hyperparathyroidism is rare in clinic. Because of occult onset and symptoms varied, misdiagnosis is made sometimes. A clear diagnosis of hyperparathyroidism and parathyroid tumors localization is the key for successful treatment. 99mTc-MDP bone scintigraphy and 99mTc -MIBI parathyroid tumor imaging has certain advantages. To be used clinically, those principal achieves can reduce misdiagnosis of primary hyperparathyroidism.

## **2. Clinical features of parathyroid adenoma**

## **2.1 Definition**

72 Soft Tissue Tumors

The right leg was dysfunction fracture of the right femur. In conclusion**,** I think that

So, I have had 99mTc-MIBI parathyroid tumor double-phase imaging. 99mTc-MIBI parathyroid tumor imaging not only can observe the shape and location, but can also

Immediate (upper) and Delayed (lower) 99mTc-MIBI imaging reveals a focus of increased activity at the inferior tip of the right lobe of the thyroid, Consistent with parathyroid

99mTc-MIBI scan showed: right lower parathyroid adenoma (Please see attached).

First, was performed parathyroid adenoma' ectomy in surgical operating theatre. Then, Reduction of fracture and internal fixation was performed by orthopedic doctor.

She was given diet and some medication advice to help her to gain full recovery. JST' doctor Peng Jing Jing etc. Primary Academic contributions to this project

< Application of Radionuclide Imaging in Diagnosis of hyperfunctioning Parathyroid tumors>journal of Chinese Nuclear Medicine Dec.2003[2] .Cited by Zhuhai City, Guangdong Province People's Hospital Chen Jiang lin etc. in Anthology of Medicine Apr.2006[5], the paper reported a case Qualitative and locational diagnosis with nuclear medicine of primary hyperparathyroidism and successful surgery of parathyroid adenoma: Peng Jingjing et al thought, there are two main features of metabolic bone disease due to hyperparathyroidism in 99mTc-MDP bone imaging: (1) Bone scan is clear showed total body as "Super Scan"; (2) Increased uptake in calvaria and jawbone for

Diagnosis:Primary hyperparathyroidism caused by a parathyroid adenoma

diagnosis is hyperparathyroidism.

adenoma.

Parathyroid adenoma

She was discharged on 1999.01.11.

display functional status for parathyroid tumor.

Fig. 4. 99mTc-MIBI parathyroid tumor (double-phase) imaging.

Ultra scan also showed: Parathyroid tumor

Metabolic bone disease Osteoporosis Dysfunction fracture (the right femur).

Mrs. Liang was given operating treatments on 1998.12.21:

Focus which lead to fracture of the right femur was brown tumor

Finally, the diagnosis in pathology (98-X1095) was:

Primary hyperparathyroidism incidence rate is about 27/100000 per year, of which 80% is parathyroid tumor, 20% is benign hyperplasia, and parathyroid carcinoma is extremely rare. Because of the parathyroid hormone (PTH) secretes more than the level required to maintain normal serum calcium concentration bring about, laboratory parameters abnormal shows hypercalcemia, hypophosphatemia, elevated alkaline phosphatase and parathyroid hormone increased.

Clinical symptoms mainly in four systems


"Super scan" of hyperparathyroidism (HPT) metabolic bone disease

Early parathyroid adenoma causing bone metabolism changes in 99mTc-MDP whole body bone scan image is generalized increased uptake with characterized by the "black skull" and very clearly as "super scan" which give expression to increased contrast between bone and soft tissue due to bone turnover speed and active bone metabolism.

Metabolic bone disease with HPTdifferent from metastasis imaging

Differential point in whole body bone scan image between "super scan" of HPT metabolic bone disease and wide range of bone metastasis is: HPT metabolic bone disease "super scan" is general uniformity high uptake in the axial skeleton and limb bones (Figure 5); and features of bone metastasis "super scan" are: high uptake of the mainly axial skeleton (Figure 6) and proximal limb bone, with point like lesions of radioactive concentration.

## **2.2 Fracture and brown tumor**

The Patient with proceeding of parathyroid tumors, X-ray radiograph shows bone resorption caused by osteoclast, and lacy cortical thinning leading to subperiosteal bone resorption, typical in middle phalanx radial side of index finger and middle finger.

Radiology images can also show brown tumor formed by micro-fracture bleeding, local accumulation of macrophages, and replacement of fibrous tissue. Brown tumor and fractures in the whole body bone scan images showed localized uptake. Large fibrocystic changes (brown tumor) can be expressed as a radioactive defect of the "cold zone" (Figure 2, the anteposition imaging shows: brown tumor in right ilium).

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 75

B-ultrasonic examination: after the diagnosis of HPT metabolic bone diseases, neck

99mTc-MIBI parathyroid tumor imaging: after the diagnosis of HPT metabolic bone diseases, the SPECT 99mTc-MIBI double-phase parathyroid tumor imaging is helpful to the localization diagnosis of parathyroid adenoma (especially ectopic parathyroid adenoma)

1. Clinical manifestations of parathyroid adenoma have diversity. There are four mainly symptoms: skeletal system, urinary tract stones, neuropsychiatric system and digestive symptoms. Bone pain and fracture is the most common complained of. Therefore, physicians and surgeons should have a basic consciousness with the diagnosis of parathyroid tumors, such as patients with long kidney stones history, have symptoms

2. Laboratory test is helpful to the diagnosis of hyperparathyroidism: calcium, phosphorus, alkaline phosphatase (AKP) and parathyroid hormone (PTH) was

3. The recognition characteristic image of the "super scan " of hyperparathyroidism in

4. Neck ultrasonography and 99mTc-MIBI double-phase parathyroid imaging can diagnose and localize parathyroid tumor clearly, which contribute to parathyroid tumor surgery.

Abnormal secretion of parathyroid hormone PTH leads to changes in bone metabolism in parathyroid tumor patients .Bone pain or dysfunction fracture are always the reason for patients to the hospital. There were many patients initially diagnosed with unilateral bone cyst (Brown tumor of fibrocystic changes in local radiology images), or misdiagnosed as bone metastases (bone scan imaging features were not yet understand). In order to accurate diagnosis and effective treatment for parathyroid tumor, it is very important to familiar with the differential diagnosis of bone scan, advances of orthopedic medical imaging basic research in molecular imaging and clinical application in bone tumors and disease as a starting point, the next section focus on the bone scan imaging features and differential diagnosis between parathyroid tumor metabolic bone disease and multiple myeloma, rickets etc. eight diseases, with the aim of doctor comprehend typical characteristic

International medical imaging community reached a consensus on the "molecular imaging"

2. "molecular imaging" observes living body (human or animal) in vivo,which can provide

1. "Molecular imaging" is the imaging embodiment for the molecular level;

**3.2 Differential diagnosis of parathyroid adenoma in clinical orthopedics** 

ultrasound is a simple and preferred method to localize the parathyroid tumors.

**3. Diagnosis and differential diagnosis of parathyroid tumor** 

99mTc-MDP whole body bone scan is very important.

**4. Advancement in fundamental researches** 

dynamic observation time-varying continuously.

New concept of orthopedic molecular imaging

**2.3 Preoperative localization of parathyroid adenoma** 

which is prepared for surgical removal.

of bone pain or fractures.

abnormal.

distinction**.** 

definition In June 2007:

**3.1 Clinical diagnosis of parathyroid adenoma** 

Fig. 5. "Super scan" with HPT metabolic bone disease

Fig. 6. "Super scan" with extensive bone metastases

## **2.3 Preoperative localization of parathyroid adenoma**

74 Soft Tissue Tumors

Fig. 5. "Super scan" with HPT metabolic bone disease

Fig. 6. "Super scan" with extensive bone metastases

B-ultrasonic examination: after the diagnosis of HPT metabolic bone diseases, neck ultrasound is a simple and preferred method to localize the parathyroid tumors.

99mTc-MIBI parathyroid tumor imaging: after the diagnosis of HPT metabolic bone diseases, the SPECT 99mTc-MIBI double-phase parathyroid tumor imaging is helpful to the localization diagnosis of parathyroid adenoma (especially ectopic parathyroid adenoma) which is prepared for surgical removal.

## **3. Diagnosis and differential diagnosis of parathyroid tumor**

## **3.1 Clinical diagnosis of parathyroid adenoma**


#### **3.2 Differential diagnosis of parathyroid adenoma in clinical orthopedics**

Abnormal secretion of parathyroid hormone PTH leads to changes in bone metabolism in parathyroid tumor patients .Bone pain or dysfunction fracture are always the reason for patients to the hospital. There were many patients initially diagnosed with unilateral bone cyst (Brown tumor of fibrocystic changes in local radiology images), or misdiagnosed as bone metastases (bone scan imaging features were not yet understand). In order to accurate diagnosis and effective treatment for parathyroid tumor, it is very important to familiar with the differential diagnosis of bone scan, advances of orthopedic medical imaging basic research in molecular imaging and clinical application in bone tumors and disease as a starting point, the next section focus on the bone scan imaging features and differential diagnosis between parathyroid tumor metabolic bone disease and multiple myeloma, rickets etc. eight diseases, with the aim of doctor comprehend typical characteristic distinction**.** 

## **4. Advancement in fundamental researches**

New concept of orthopedic molecular imaging

International medical imaging community reached a consensus on the "molecular imaging" definition In June 2007:


Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 77

18F-FDG imaging (SPECT/CT) to detect what primary carcinoma lesion is from and location for biopsy pathological confirmed diagnosis metastatic carcinoma[10] FIGURE.8, to solve the

Primary Academic contributions to this project《Application of Radionuclide Imaging in Osteosarcoma》[11]Cited by Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Feng Guo-wei etc. reported a case bone scan uptake 99mTc-MDP increased appearance in aggressive osteosarcoma with pleural,lung metastases demonstrated by operative pathological specimen[13]: Using SPECT Imaging and Molecular probe with tracer 99mTc-MDP, After following up 133 patients with osteosarcoma,Peng Jingjing et al thought, 99mTc-MDP SPECT images for detection of pulmonary and bone metastases and recurrent is useful. The usefulness of bone scintigraphy is overall in that is more sensitive than radiograph, X-ray and bone scan may be complementary in favor of the patients diagnoses,

(A) (B)

For unknown primary tumor of bone metastases performed PET/CT scan is necessary because of variety of 18F-FDG, a sensitive tracer of malignant tumor, to identify the primary tumor so that patients can receive timely treatment. Unknown primary metastatic tumors occur in approximately 5% to 6.5%, according to report at least 1 / 3 of patients with PET

Fig. 7. Bone scan showed Osteosarcoma focus for 99mTc-MDP positive imaging tracing metastases in bone and lymph node with surgical pathology confirmed (A) and recurrence

detected the primary lesion, in which patients receive accurate and timely treatment.

medical difficult problem.

treatment and follow up.

indication after operation (B).

3. "molecular imaging" can be detected by means of instruments (such as PCT/CT and MRI, etc. equipment) and can be quantitative.

The theoretical development of orthopedic molecular imaging was based on the new understanding of bone anatomy and physiology.

Bone structure of normal adult bone can be summarized in four categories [6]:

Gross level

The skeleton consists of two major parts, the axial skeleton includes the skull, spine and rib cage (ribs and sternum), while the appendicular skeleton includes the bones of the extremities, pelvic girdle and pectoral girdle (clavicles and scapulae)

Tissue level

Bone is divided into two types of tissues forming the skeleton: compact or cortical bone and cancelous, trabecular or spongy bone. The compact bone constitutes 80% of the skeletal mass. The appendicular skeleton is composed predominantly of contical bone. The cortical bone is thicker in the diaphysis. The blood supply to the metaphysic is rich. The spine is composed predominantly of cancellous bone in the body of the vertebra and compact bone in the endplates and posterior elements. The spongy bone has a turnover rate approximately eight times greater than the cortical bones and hosts hematopoietic cells and many blood cells.

#### **Cellular lever**

Three types of cells can be seen in bone: osteoblasts, which produce the organic bone matrix; osteocytes, which produce the inorganic matrix; osteoclasts, which are active in bone resorption. Osteoclasts are derived from the hemopoietic system, in contrast to the mesenchymal origin of osteoblasts. Osteocytes are derived from osteoblasts that have secreted bone matrix around themselves.

#### **Molecular level**

At the Molecular level, bone matrix is composed primarily of organic matrix (approximately 35%), including collagen and glycoproteins, and inorganic matrix (approximately 65%), which includes hydroxyapatite, cations (calcium, magnesium, sodium, potassium and strontium) and anions (fluoride, phosphorus and chloride). The calcium in inorganic matrix of bone provid hardness to withstand pressure, and the collagen fibers in organic components provide support and tension.

99mTc-MDP bone scan can embodiment changes in the pathogenesis of the human body on the molecular level, and it is detected by SPECT, three phase imaging for patient examine dynamic change with time varying and may performed semi—quantitative analysis for lesion,so bone scan is part of within the domain of molecular imaging [7]. Orthopedic Nuclear Medicine constitutes an important component of orthopedic molecular imaging. Recent Advances in Orthopedics Combined Medical Imaging with Clinical Practice are important to the development of molecular imaging and rich of content [8, 9], [7, 10].

For example, using isotopic tracer 99mTc-MDP as a molecular probe we can tracer the oncology biological behavior of osteosarcoma[11],Bone scan can detect multiple lesions of osteosarcoma, show the lung,bone and lymph node metastasis FIGURE.7(A), and provide postoperative follow-up for painful body differential diagnosis recurrence from prosthetic loose FIGURE.7 (B) and efficacy evaluation of chemotherapy. Chemotherapy efficacy for osteosarcoma before operation may be evaluted by quantitative study of 18F-FDG [12], and

3. "molecular imaging" can be detected by means of instruments (such as PCT/CT and

The theoretical development of orthopedic molecular imaging was based on the new

The skeleton consists of two major parts, the axial skeleton includes the skull, spine and rib cage (ribs and sternum), while the appendicular skeleton includes the bones of the

Bone is divided into two types of tissues forming the skeleton: compact or cortical bone and cancelous, trabecular or spongy bone. The compact bone constitutes 80% of the skeletal mass. The appendicular skeleton is composed predominantly of contical bone. The cortical bone is thicker in the diaphysis. The blood supply to the metaphysic is rich. The spine is composed predominantly of cancellous bone in the body of the vertebra and compact bone in the endplates and posterior elements. The spongy bone has a turnover rate approximately eight times greater than the cortical bones and hosts hematopoietic cells and many blood

Three types of cells can be seen in bone: osteoblasts, which produce the organic bone matrix; osteocytes, which produce the inorganic matrix; osteoclasts, which are active in bone resorption. Osteoclasts are derived from the hemopoietic system, in contrast to the mesenchymal origin of osteoblasts. Osteocytes are derived from osteoblasts that have

At the Molecular level, bone matrix is composed primarily of organic matrix (approximately 35%), including collagen and glycoproteins, and inorganic matrix (approximately 65%), which includes hydroxyapatite, cations (calcium, magnesium, sodium, potassium and strontium) and anions (fluoride, phosphorus and chloride). The calcium in inorganic matrix of bone provid hardness to withstand pressure, and the collagen fibers in organic

99mTc-MDP bone scan can embodiment changes in the pathogenesis of the human body on the molecular level, and it is detected by SPECT, three phase imaging for patient examine dynamic change with time varying and may performed semi—quantitative analysis for lesion,so bone scan is part of within the domain of molecular imaging [7]. Orthopedic Nuclear Medicine constitutes an important component of orthopedic molecular imaging. Recent Advances in Orthopedics Combined Medical Imaging with Clinical Practice are

For example, using isotopic tracer 99mTc-MDP as a molecular probe we can tracer the oncology biological behavior of osteosarcoma[11],Bone scan can detect multiple lesions of osteosarcoma, show the lung,bone and lymph node metastasis FIGURE.7(A), and provide postoperative follow-up for painful body differential diagnosis recurrence from prosthetic loose FIGURE.7 (B) and efficacy evaluation of chemotherapy. Chemotherapy efficacy for osteosarcoma before operation may be evaluted by quantitative study of 18F-FDG [12], and

important to the development of molecular imaging and rich of content [8, 9], [7, 10].

Bone structure of normal adult bone can be summarized in four categories [6]:

extremities, pelvic girdle and pectoral girdle (clavicles and scapulae)

MRI, etc. equipment) and can be quantitative.

understanding of bone anatomy and physiology.

secreted bone matrix around themselves.

components provide support and tension.

Gross level

Tissue level

cells.

**Cellular lever** 

**Molecular level** 

18F-FDG imaging (SPECT/CT) to detect what primary carcinoma lesion is from and location for biopsy pathological confirmed diagnosis metastatic carcinoma[10] FIGURE.8, to solve the medical difficult problem.

Primary Academic contributions to this project《Application of Radionuclide Imaging in Osteosarcoma》[11]Cited by Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Feng Guo-wei etc. reported a case bone scan uptake 99mTc-MDP increased appearance in aggressive osteosarcoma with pleural,lung metastases demonstrated by operative pathological specimen[13]: Using SPECT Imaging and Molecular probe with tracer 99mTc-MDP, After following up 133 patients with osteosarcoma,Peng Jingjing et al thought, 99mTc-MDP SPECT images for detection of pulmonary and bone metastases and recurrent is useful. The usefulness of bone scintigraphy is overall in that is more sensitive than radiograph, X-ray and bone scan may be complementary in favor of the patients diagnoses, treatment and follow up.

Fig. 7. Bone scan showed Osteosarcoma focus for 99mTc-MDP positive imaging tracing metastases in bone and lymph node with surgical pathology confirmed (A) and recurrence indication after operation (B).

For unknown primary tumor of bone metastases performed PET/CT scan is necessary because of variety of 18F-FDG, a sensitive tracer of malignant tumor, to identify the primary tumor so that patients can receive timely treatment. Unknown primary metastatic tumors occur in approximately 5% to 6.5%, according to report at least 1 / 3 of patients with PET detected the primary lesion, in which patients receive accurate and timely treatment.

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 79

pediatrics orthopedic department. Importantly, which eliminate the burden of mind for the patients without serious diseases. Application of the research findings for imaging diagnoses can not only exclude the difficulty and anxiety for patients and get the suitable cure in a timely manner, but also provide the effective way for acquire the best

The bone scans imaging differential diagnosis of parathyroid adenoma there are eight of typical image patterns which a doctor should be familiar with in clinical diagnoses. Have you had an knowledge of thereinafter imaging diagnoses Trained continued medical

【case report】 Female patient, 29 years old complaining of pain in low back and both knees for 4 years, lower extremity weakness, vomiting and kidney stones 2 years. X-ray film showed severe osteoporosis, and fracture of the right pubic bone. 【The results of tests】Ca ↑ 3.27 mmol / L (2.25 ~ 2.75), P ↓ 0.78 mmol / L (0.8 ~ 1.6), AKP ↑

**5.1 Primary hyperparathyroidism caused by a parathyroid adenoma** 

1002 mmol / L (25 ~ 90), parathyroid hormone (PTH) ↑ 70.1 (0.8 ~ 3.9)

Fig. 9. 99mTc-MDP Bone scan showed metabolic disease with HPT

economy and social performance.

education[4]?

Metabolic bone disease

【99mTc-MDP Bone scan】

Fig. 8. 18F-FDG SPECT/CT detecting the primary carcinoma lesion and location for pathological confirmed lumbar spine metastatic carcinoma.

99mTc-MDP bone scan (left) seen in single lumbar spine bone tumor which by hospital after operation surgical pathology confirmed metastatic carcinoma, primary tumor is unknown. By 18F-FDG SPECT / CT imaging (right) to detect the primary lesion, located in the liver, so the patient performed a specific liver therapy.

## **5. Application of molecular imaging in diagnosis of orthopedic diseases**

In the difficult diagnosis of puzzle patients and treatment, bring forth diagnostic 99mTc-MDP bone scan new ideas were a positive contribution to the pati. Difficult diagnosed patients were abnormal in bone scan, X-ray film, CT, or magnetic resonance imaging, but failed to identify problems .What is the real illness cause? Doctor must timely and accurate answers to diagnostic questions. Famous Beijing JST Hospital is the first choice for patients from all over the country whose first symptoms are bone pain and pathologic (or insufficiency) fractures.

JST' hospital doctors through a long period of careful clinical research improved the cognitive level of medical images, bringing the new ideas in Molecular Imaging in Diagnosis of Orthopedic Diseases. We summed up the imaging features diagnosis law of parathyroid tumor, and differentiate diagnosis regular pattern from other diseases on bone scan, used the scientific theory to guide clinical practice.

The patients complained of bone pain for unknown reasons. Fracture was diagnosed accurately by the bone scan. Patients diagnosed with metabolic bone disease primary hyperparathyroidism were treated with surgically removing of parathyroidoma, metabolic bone diseases by secondary hyperparathyroidism such as renal osteopathy or Rickets went to department of internal medicine treatment. Patients diagnosed with Multiple myeloma were treated in the hematology department. Patients diagnosed with articular disease were treated in the orthopedics [14] or rheumatology department. Patients diagnosed with benign or malignant bone primary tumor or bone disease were treated in bone oncology or pediatrics orthopedic department. Importantly, which eliminate the burden of mind for the patients without serious diseases. Application of the research findings for imaging diagnoses can not only exclude the difficulty and anxiety for patients and get the suitable cure in a timely manner, but also provide the effective way for acquire the best economy and social performance.

The bone scans imaging differential diagnosis of parathyroid adenoma there are eight of typical image patterns which a doctor should be familiar with in clinical diagnoses. Have you had an knowledge of thereinafter imaging diagnoses Trained continued medical education[4]?

## **5.1 Primary hyperparathyroidism caused by a parathyroid adenoma**

#### Metabolic bone disease

78 Soft Tissue Tumors

Fig. 8. 18F-FDG SPECT/CT detecting the primary carcinoma lesion and location for

99mTc-MDP bone scan (left) seen in single lumbar spine bone tumor which by hospital after operation surgical pathology confirmed metastatic carcinoma, primary tumor is unknown. By 18F-FDG SPECT / CT imaging (right) to detect the primary lesion, located in the liver, so

**5. Application of molecular imaging in diagnosis of orthopedic diseases** 

the country whose first symptoms are bone pain and pathologic (or insufficiency) fractures.

In the difficult diagnosis of puzzle patients and treatment, bring forth diagnostic 99mTc-MDP bone scan new ideas were a positive contribution to the pati. Difficult diagnosed patients were abnormal in bone scan, X-ray film, CT, or magnetic resonance imaging, but failed to identify problems .What is the real illness cause? Doctor must timely and accurate answers to diagnostic questions. Famous Beijing JST Hospital is the first choice for patients from all over

JST' hospital doctors through a long period of careful clinical research improved the cognitive level of medical images, bringing the new ideas in Molecular Imaging in Diagnosis of Orthopedic Diseases. We summed up the imaging features diagnosis law of parathyroid tumor, and differentiate diagnosis regular pattern from other diseases on bone

The patients complained of bone pain for unknown reasons. Fracture was diagnosed accurately by the bone scan. Patients diagnosed with metabolic bone disease primary hyperparathyroidism were treated with surgically removing of parathyroidoma, metabolic bone diseases by secondary hyperparathyroidism such as renal osteopathy or Rickets went to department of internal medicine treatment. Patients diagnosed with Multiple myeloma were treated in the hematology department. Patients diagnosed with articular disease were treated in the orthopedics [14] or rheumatology department. Patients diagnosed with benign or malignant bone primary tumor or bone disease were treated in bone oncology or

pathological confirmed lumbar spine metastatic carcinoma.

scan, used the scientific theory to guide clinical practice.

the patient performed a specific liver therapy.

【case report】 Female patient, 29 years old complaining of pain in low back and both knees for 4 years, lower extremity weakness, vomiting and kidney stones 2 years. X-ray film showed severe osteoporosis, and fracture of the right pubic bone. 【The results of tests】Ca ↑ 3.27 mmol / L (2.25 ~ 2.75), P ↓ 0.78 mmol / L (0.8 ~ 1.6), AKP ↑ 1002 mmol / L (25 ~ 90), parathyroid hormone (PTH) ↑ 70.1 (0.8 ~ 3.9) 【99mTc-MDP Bone scan】

Fig. 9. 99mTc-MDP Bone scan showed metabolic disease with HPT

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 81

"Super scan" caused by extensive bone and marrow metastasis is different from the one caused by metabolic bone disease with hyperparathyroidism. The metastasis' Super scan is characterized by diffuse uptake of lesions mainly located in the axial skeleton and proximal

In hyperparathyroidism resulting in metabolic bone disease, "Super scan" is involving the entire bone. "The black skull" is obviously. Radioactivity distributes diffusely and evenly.

Hypertrophic Osteoarthropathy caused by Secondary form intrathoracic pathological condition which is a form of periostitis and may be painful. Tubular bones may show periosteal new bone formation. This pathological feature explains the typical bone scan pattern of diffusely increased uptake along the cortical margins of long bones giving the

Fig. 12. Hypertrophic Pulmonary Osteoarthropathy:The parallel track pattern

with a parallel track pattern in the ulna-radius and tibiae.

**5.4 Multiple Myeloma (MM)** 

skull and proximal long bone.

Hypertrophic Pulmonary Osteoarthropathy in a patient with left lung hilum mass.

Note the diffusely increased uptake in all bones of the upper extremity and lower extremity

Bone scan of MM shows "the same disease with different characteristics images". The patient's image can have many manifestations: multiple uptake Increase strip or banding, decreased uptake cold spot lesions [15], which mainly distribute in the spine, pelvis, ribs,

In clinical work, some MM bone scan image does not show the bone destruction, so bone scan revealed no abnormalities. Imaging physicians and orthopedic surgeons should pay attention to the patient's complain for bone pain, considering for multiple myeloma.

limbs, which can be spotty radioactivity concentration.

**5.3 Hypertrophic Osteoarthropathy** 

appearance of "parallel tracks".

Whole body bone scan

After Intravenous imaging agent 99mTc-MDP 20mCi 3 hours, whole body bone scan was obtained (Fig. 9.) Bone image is very clearly. The skull showed increased radioactivity universal distribution. Axial skeleton and limb bones are visible with increased uptake - "super scan" of hyperparathyroidism Metabolism Bone disease; local increased radioactivity at the fracture site in the right pubic bone. Renal imaging was light, for radiation occlusion in double renal pelvis due to kidney stones with urinary obstruction.

【neck ultrasound】no seen abnormal in thyroid

【diagnosis 】Ectopic parathyroid adenoma

【Treatment】 Surgical resection of ectopic parathyroid adenoma.

Two years later, the patient recovered.

Fig. 10. 99mTc -MIBI parathyroid tumor imaging

99mTc-MIBI double-phase parathyroid tumor imaging: Early image (A)shows, the position and morphology of double-leaf thyroid were normal. The abnormal radioactive uptake can be seen on the right side below thyroid, the lower edge of which was close to the level of sternum .The size is about 3.8cm × 2.4cm. Delayed image (B) showed the thyroid image faded, and the oval-shaped abnormal lesion is still visible below the right side of thyroid.

## **5.2 Metastases "Super scan"**

Fig. 11. Bone and bone marrows Metastases from poorly differentiated adenocarcinoma.

"Super scan" caused by extensive bone and marrow metastasis is different from the one caused by metabolic bone disease with hyperparathyroidism. The metastasis' Super scan is characterized by diffuse uptake of lesions mainly located in the axial skeleton and proximal limbs, which can be spotty radioactivity concentration.

In hyperparathyroidism resulting in metabolic bone disease, "Super scan" is involving the entire bone. "The black skull" is obviously. Radioactivity distributes diffusely and evenly.

## **5.3 Hypertrophic Osteoarthropathy**

80 Soft Tissue Tumors

After Intravenous imaging agent 99mTc-MDP 20mCi 3 hours, whole body bone scan was obtained (Fig. 9.) Bone image is very clearly. The skull showed increased radioactivity universal distribution. Axial skeleton and limb bones are visible with increased uptake - "super scan" of hyperparathyroidism Metabolism Bone disease; local increased radioactivity at the fracture site in the right pubic bone. Renal imaging was light, for radiation occlusion

(A)15MIN (B)2HR

99mTc-MIBI double-phase parathyroid tumor imaging: Early image (A)shows, the position and morphology of double-leaf thyroid were normal. The abnormal radioactive uptake can be seen on the right side below thyroid, the lower edge of which was close to the level of sternum .The size is about 3.8cm × 2.4cm. Delayed image (B) showed the thyroid image faded, and the oval-shaped abnormal lesion is still visible below the right side of thyroid.

Fig. 11. Bone and bone marrows Metastases from poorly differentiated adenocarcinoma.

in double renal pelvis due to kidney stones with urinary obstruction.

【Treatment】 Surgical resection of ectopic parathyroid adenoma.

【neck ultrasound】no seen abnormal in thyroid 【diagnosis 】Ectopic parathyroid adenoma

Fig. 10. 99mTc -MIBI parathyroid tumor imaging

**5.2 Metastases "Super scan"** 

Two years later, the patient recovered.

Whole body bone scan

Hypertrophic Osteoarthropathy caused by Secondary form intrathoracic pathological condition which is a form of periostitis and may be painful. Tubular bones may show periosteal new bone formation. This pathological feature explains the typical bone scan pattern of diffusely increased uptake along the cortical margins of long bones giving the appearance of "parallel tracks".

Fig. 12. Hypertrophic Pulmonary Osteoarthropathy:The parallel track pattern

Hypertrophic Pulmonary Osteoarthropathy in a patient with left lung hilum mass.

Note the diffusely increased uptake in all bones of the upper extremity and lower extremity with a parallel track pattern in the ulna-radius and tibiae.

#### **5.4 Multiple Myeloma (MM)**

Bone scan of MM shows "the same disease with different characteristics images". The patient's image can have many manifestations: multiple uptake Increase strip or banding, decreased uptake cold spot lesions [15], which mainly distribute in the spine, pelvis, ribs, skull and proximal long bone.

In clinical work, some MM bone scan image does not show the bone destruction, so bone scan revealed no abnormalities. Imaging physicians and orthopedic surgeons should pay attention to the patient's complain for bone pain, considering for multiple myeloma.

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 83

Fig. 14. Fibrous dysplasia (A) monostotic the right femur (B) polyostotic for whole body bone

Whole body bone scan used for overlook the Fibrous dysplasia condition present as solitary

Rheumatoid Arthritis is the autoimmune disease causes inflammation of the connective tissue mainly in the joints. Synovitis activity is the dominant clinical variable that determines the therapeutic approachin patients with rheumatoid arthritis. 99mTc-MDP bone scan used for overlook the all joint to measure the condition present of synovitis activity and

Bone scan image show intensely increased uptake in lesion bones.

differential diagnosis from other diseases result in bone-joint pain.

lesion (monostotic) or with multiple foci (polyostotic).

Fig. 15. Rheumatoid Arthritis Synovitis activity

**5.6 Rheumatoid Arthritis** 

Patient's relevant laboratory tests, bone pain, anemia, infection and renal dysfunction and related organ or tissue damage (ROTI) should be recorded.

Fig. 13. Multiple Myeloma (MM) multiple striping or banding increased uptake with Spinal is the most common image pattern and the typical image pattern of decreased uptake "Cold spot" lesions on 99mTc-MDP Bone scan (Note the "Cold spot" lesions in sternum)

#### **5.5 Fibrous dysplasia**

Fibrous dysplasia is a benign bone disorder which remains essentially unchanged and can be seen in lesion of long duration. The lesions cause thining of the bone cortex and replacement marrow.

The condition may present as solitary lesion (monostotic) or with multiple foci (polyostotic). Polyostotic fibrous dysplasia may be associated with café-au-lait pigmentation and multiple endocrine hyperfunction, most commonly seen as precocious puberty in girls, Cushing's syndrome, and is called the McCune-Albrightzonght syndrome.

Standard radiographs show lucent areas with various amounts of ossification and cyst formation and may show expansion. Fibrous dysplasia, in general appears as an area of markedly increased uptake on 99mTc-MDP bone scan.

Fig. 14. Fibrous dysplasia (A) monostotic the right femur (B) polyostotic for whole body bone

Bone scan image show intensely increased uptake in lesion bones.

Whole body bone scan used for overlook the Fibrous dysplasia condition present as solitary lesion (monostotic) or with multiple foci (polyostotic).

#### **5.6 Rheumatoid Arthritis**

82 Soft Tissue Tumors

Patient's relevant laboratory tests, bone pain, anemia, infection and renal dysfunction and

Fig. 13. Multiple Myeloma (MM) multiple striping or banding increased uptake with Spinal is the most common image pattern and the typical image pattern of decreased uptake "Cold

Fibrous dysplasia is a benign bone disorder which remains essentially unchanged and can be seen in lesion of long duration. The lesions cause thining of the bone cortex and

The condition may present as solitary lesion (monostotic) or with multiple foci (polyostotic). Polyostotic fibrous dysplasia may be associated with café-au-lait pigmentation and multiple endocrine hyperfunction, most commonly seen as precocious puberty in girls, Cushing's

Standard radiographs show lucent areas with various amounts of ossification and cyst formation and may show expansion. Fibrous dysplasia, in general appears as an area of

spot" lesions on 99mTc-MDP Bone scan (Note the "Cold spot" lesions in sternum)

syndrome, and is called the McCune-Albrightzonght syndrome.

markedly increased uptake on 99mTc-MDP bone scan.

**5.5 Fibrous dysplasia** 

replacement marrow.

related organ or tissue damage (ROTI) should be recorded.

Rheumatoid Arthritis is the autoimmune disease causes inflammation of the connective tissue mainly in the joints. Synovitis activity is the dominant clinical variable that determines the therapeutic approachin patients with rheumatoid arthritis. 99mTc-MDP bone scan used for overlook the all joint to measure the condition present of synovitis activity and differential diagnosis from other diseases result in bone-joint pain.

Fig. 15. Rheumatoid Arthritis Synovitis activity

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 85

Bone scintigraphy scan shows metabolic bone disease. Note there are ribbon-like zones multiple foci increased uptake in rib cage caused by pseudofractures on bone scans mimicking metastatic bone disease. This characterstic pseudofractures is one of specific

The presence of Looser's zones, also called Pseudofractures or Milkman's fractures, there are ribbon-like zones increased uptake in rib cage, pelvis, right distal femora、tibia,Bilateral metatarsals and spinal column, Long-standing Osteomalacia result in characteristic

We recommended further examination: 1.25-dihydroxyvitamin D3 [1, 25 - (OH) 2D3] 26.75pg/ml (26 -65pg/ml), Parathyroid hormone PTH ↑ 84.6 pg / ml (8.3 -68.0), 24-hour

Diagnosis: The patient was diagnosed as hypophosphatemic rickets based on the fact of middle-aged male patients with chronic process. The bone pain and muscle weakness was the main manifestation, which progressively increased and lead to movement disorder. Laboratory tests: normal calcium, hypophosphatemia and elevated ALP. Bone scan with pseudo fractures are the characteristic of bone scan imaging finding prompted rickets. The diagnosis of hypophosphatemic rickets was established. Increased PTH caused by

After three years of out-patient and hospital treatment, this patient has been able to work

The patient's 99mTc-MDP bone scan image shows the pseudofeatures of metabolic bone disease: rib pseudofracture site showed local radioactivity uptake; ribbon-like zones increased uptake in spine, pelvis and lower extremities which embodiment Osteomalacia

Rickets refers that bone matrix of adults whose epiphyseal growth plate has been closed mineralized impediently. It is a metabolic bone disease that newly formed bone matrix is not mineralized in the normal manner. There are many causes responsible for decreased extracellular calcium phosphate product, and resulted in bone mineral deposition obstacles. The clinical manifestations of rickets are mainly bone pain and muscle weakness, fractures and deformities. Metabolic bone disease, pseudo fractures are the characteristic of bone scan

Rickets belongs to endocrine and metabolic diseases. Now there are many related diseases, including seven sets of issues: Associated with vitamin D endocrine system diseases, phosphate balance abnormalities, metabolic acidosis, abnormal calcium balance, bone matrix abnormalities, lack of primary mineralization, some factors leading to the inhibition of mineralization. Although the clinical presentation is similar, but the pathogenic mechanisms are different, relating biochemical laboratory examination and treatment are also different. Therefore, in the diagnosis of rickets, we need the systematic, in-depth inspection and analysis to clarify the etiology. Diagnosis and treatment guide of rickets

A 54 years old male patient, complained of "left knee pain, glided into varus deformity leg 4 years, left muscle atrophy, walking inconvenience", were diagnosed as Paget's Osteitis by

abnormality of Rickets.

properly.

imaging finding.

refers to Cecil Medicine.

pathology.

**5.8 Paget's disease (Osteitis deformans)** 

Biconcave collapsed vertebrae.

urine calcium 0.36mmol, urinary phosphorus 38.13mmol.

reflect the pathological changes of pseudofracture in rickets.

hyperparathyroidism was secondary to rickets.

A 52 years old female patient, suffered from rheumatoid arthritis 4 years. The left knee was painful and deformed for six months. TKA was done. Whole body bone scan showed that left knee joint was after treated by replacement surgery, and rheumatoid arthritis (active phase) violated elbows, wrists, hands, hips, knees, feet and thoracic and lumbar spine with Increase uptake in the areas of the joints affected Synovitis activity.

## **5.7 Rickets**

A 41-year-old male patient suffered from joint pain and back pain more than 5 years and his lower limbs were weakening gradually for 1 year. The patient suffered from intermittent back pain with no obvious incentive for 5 years, more severe in the morning.It was also accompanied by joint stiffness, which reduced after the event, and did not affect the activities. Initially he was treated at a local hospital as rheumatoid arthritis, the pain releived. But in the past 2 years, the pain gradually got worse, double shoulder, hips, chest, leg were painful and weak. He was bound to bed, get up on stage difficultly. He was 7cm lower then when he was young.

Tests carried out and The results showed

Serum calcium (Ca) 2.4mmol / L (2.25-2.75)

Serum phosphorus (P) ↓ 0.53mmol / L (0.8-1.6)

Alkaline phosphatase (AKP) ↑ 480 IU / L (25-90)

Rheumatoid factor (RF)-negative

HLA-B27- negative

A/G were normal, renal function BUN, CRE, UA mused in the normal range.

Spine X-ray showed osteoporosis. MRI reported suspected pelvis bone destruction. Whole body bone scan (Figure16) shows skeletal clearly: Bilateral ribs show multiple hot spots, as "beaded ribs"; the spine shows multiple vertebral collapse as strip change; The agent 99mTc-MDP uptake in shoulders is increased, and the left is more; There are ribbon-like zones increased uptake in rib cage, pelvis, femora, tibia and metatarsals. Bone scintigraphy scan shows metabolic bone disease: A specific abnormality of the rickets is the presence of Looser's zones, also called Pseudofractures or Milkman's fractures.

Fig. 16. Diagnostic Imaging feature of Rickets

A 52 years old female patient, suffered from rheumatoid arthritis 4 years. The left knee was painful and deformed for six months. TKA was done. Whole body bone scan showed that left knee joint was after treated by replacement surgery, and rheumatoid arthritis (active phase) violated elbows, wrists, hands, hips, knees, feet and thoracic and lumbar spine with

A 41-year-old male patient suffered from joint pain and back pain more than 5 years and his lower limbs were weakening gradually for 1 year. The patient suffered from intermittent back pain with no obvious incentive for 5 years, more severe in the morning.It was also accompanied by joint stiffness, which reduced after the event, and did not affect the activities. Initially he was treated at a local hospital as rheumatoid arthritis, the pain releived. But in the past 2 years, the pain gradually got worse, double shoulder, hips, chest, leg were painful and weak. He was bound to bed, get up on stage difficultly. He was 7cm

Increase uptake in the areas of the joints affected Synovitis activity.

A/G were normal, renal function BUN, CRE, UA mused in the normal range.

Looser's zones, also called Pseudofractures or Milkman's fractures.

Spine X-ray showed osteoporosis. MRI reported suspected pelvis bone destruction. Whole body bone scan (Figure16) shows skeletal clearly: Bilateral ribs show multiple hot spots, as "beaded ribs"; the spine shows multiple vertebral collapse as strip change; The agent 99mTc-MDP uptake in shoulders is increased, and the left is more; There are ribbon-like zones increased uptake in rib cage, pelvis, femora, tibia and metatarsals. Bone scintigraphy scan shows metabolic bone disease: A specific abnormality of the rickets is the presence of

**5.7 Rickets** 

lower then when he was young.

Rheumatoid factor (RF)-negative

HLA-B27- negative

Tests carried out and The results showed Serum calcium (Ca) 2.4mmol / L (2.25-2.75) Serum phosphorus (P) ↓ 0.53mmol / L (0.8-1.6) Alkaline phosphatase (AKP) ↑ 480 IU / L (25-90)

Fig. 16. Diagnostic Imaging feature of Rickets

Bone scintigraphy scan shows metabolic bone disease. Note there are ribbon-like zones multiple foci increased uptake in rib cage caused by pseudofractures on bone scans mimicking metastatic bone disease. This characterstic pseudofractures is one of specific abnormality of Rickets.

The presence of Looser's zones, also called Pseudofractures or Milkman's fractures, there are ribbon-like zones increased uptake in rib cage, pelvis, right distal femora、tibia,Bilateral metatarsals and spinal column, Long-standing Osteomalacia result in characteristic Biconcave collapsed vertebrae.

We recommended further examination: 1.25-dihydroxyvitamin D3 [1, 25 - (OH) 2D3] 26.75pg/ml (26 -65pg/ml), Parathyroid hormone PTH ↑ 84.6 pg / ml (8.3 -68.0), 24-hour urine calcium 0.36mmol, urinary phosphorus 38.13mmol.

Diagnosis: The patient was diagnosed as hypophosphatemic rickets based on the fact of middle-aged male patients with chronic process. The bone pain and muscle weakness was the main manifestation, which progressively increased and lead to movement disorder. Laboratory tests: normal calcium, hypophosphatemia and elevated ALP. Bone scan with pseudo fractures are the characteristic of bone scan imaging finding prompted rickets. The diagnosis of hypophosphatemic rickets was established. Increased PTH caused by hyperparathyroidism was secondary to rickets.

After three years of out-patient and hospital treatment, this patient has been able to work properly.

The patient's 99mTc-MDP bone scan image shows the pseudofeatures of metabolic bone disease: rib pseudofracture site showed local radioactivity uptake; ribbon-like zones increased uptake in spine, pelvis and lower extremities which embodiment Osteomalacia reflect the pathological changes of pseudofracture in rickets.

Rickets refers that bone matrix of adults whose epiphyseal growth plate has been closed mineralized impediently. It is a metabolic bone disease that newly formed bone matrix is not mineralized in the normal manner. There are many causes responsible for decreased extracellular calcium phosphate product, and resulted in bone mineral deposition obstacles. The clinical manifestations of rickets are mainly bone pain and muscle weakness, fractures and deformities. Metabolic bone disease, pseudo fractures are the characteristic of bone scan imaging finding.

Rickets belongs to endocrine and metabolic diseases. Now there are many related diseases, including seven sets of issues: Associated with vitamin D endocrine system diseases, phosphate balance abnormalities, metabolic acidosis, abnormal calcium balance, bone matrix abnormalities, lack of primary mineralization, some factors leading to the inhibition of mineralization. Although the clinical presentation is similar, but the pathogenic mechanisms are different, relating biochemical laboratory examination and treatment are also different. Therefore, in the diagnosis of rickets, we need the systematic, in-depth inspection and analysis to clarify the etiology. Diagnosis and treatment guide of rickets refers to Cecil Medicine.

## **5.8 Paget's disease (Osteitis deformans)**

A 54 years old male patient, complained of "left knee pain, glided into varus deformity leg 4 years, left muscle atrophy, walking inconvenience", were diagnosed as Paget's Osteitis by pathology.

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 87

The treatment of post-traumatic critically ill patients with acute pulmonary embolism (APE) In Nov. 10, 2000, a 56-year-old man fell from 3 meters high and got multiple traumas (Right hip fracture, fracture of the right pubis ischium branch, open comminuted fracture of the right olecranon). On Nov. 20, when the patient received second operation of open reduction and plate fixation for the right fracture acetabular under general anesthesia, he had chest tightness, shortness of breath, PaO2 critical situation of declining. Orthopedic surgery was stopped and the rescue was implemented in the ICU ward immediately. ECG shows sinus tachycardia and S�Q� T� & V1rsr 'wave, which was believed to be acute pulmonary embolism. Lung perfusion ECT was done for the patient immediately in nuclear medicine

99mTc-MAA Lung perfusion Imaging showed lung with morphologic abnormalities. Right lung was lobe and segmental perfusion defects, and left lung shows segmental perfusion defects (figure 18). With normal X-ray before surgery (Nov. 18), V / Q diagnosis was doneacute pulmonary embolism. In the ICU ward the patient received anticoagulation and thrombolytic therapy. 2 weeks later (Dec. 4), pulmonary perfusion imaging (Figure 19) was reviewed, the original lobe and segmental perfusion defects had been seen the distribution of perfusion and lung morphology was normal after effectively treatment. X-ray and ECG were normal too. The patient was pulled through by accurate diagnoses and effective

Fig. 18. Lung perfusion imaging of post-traumatic acute pulmonary embolism

department.

treatment.

Whole body bone scan showed characteristic bone expansion changes: left tibia was bending deformity; T4 vertebral body, left pelvis and tibia in the active stage of osteolysis which osteogenesis showed increased uptake. The radioactivity distribution of the left humerus was mild and uniform in sclerotic phase.

Fig. 17. Diagnostic Imaging of Paget's disease

Bone scintigraphy scan shows increased uptake in the left tibia with bending deformation**,** T4 and left pelvis with enlargement and bending deformans of the bones affected with lytic the active phase. The Left humerus shows no abnormal uptake of the radiopharmaceuticals with time on the sclerotic phase indicating a relatively inactive lesion.

## **6. Ensure patient safety preventing traumatic complication Acute Pulmonary Embolism (APE)**

Beijing Ji Shui Tan Hospital is a large modern comprehensive hospital which focuses on Orthopadic and traumatology. The surgical volume reached 35000 in 2009. Clinical research in medical imaging make a positive contribution for the protection of medical quality and patient safety, during the process of exploring critical and difficult orthopadic patients and optimize the efficacy of the diagnosis.

Whole body bone scan showed characteristic bone expansion changes: left tibia was bending deformity; T4 vertebral body, left pelvis and tibia in the active stage of osteolysis which osteogenesis showed increased uptake. The radioactivity distribution of the left humerus

Bone scintigraphy scan shows increased uptake in the left tibia with bending deformation**,** T4 and left pelvis with enlargement and bending deformans of the bones affected with lytic the active phase. The Left humerus shows no abnormal uptake of the radiopharmaceuticals

**6. Ensure patient safety preventing traumatic complication Acute Pulmonary** 

Beijing Ji Shui Tan Hospital is a large modern comprehensive hospital which focuses on Orthopadic and traumatology. The surgical volume reached 35000 in 2009. Clinical research in medical imaging make a positive contribution for the protection of medical quality and patient safety, during the process of exploring critical and difficult orthopadic patients and

with time on the sclerotic phase indicating a relatively inactive lesion.

was mild and uniform in sclerotic phase.

Fig. 17. Diagnostic Imaging of Paget's disease

optimize the efficacy of the diagnosis.

**Embolism (APE)** 

The treatment of post-traumatic critically ill patients with acute pulmonary embolism (APE) In Nov. 10, 2000, a 56-year-old man fell from 3 meters high and got multiple traumas (Right hip fracture, fracture of the right pubis ischium branch, open comminuted fracture of the right olecranon). On Nov. 20, when the patient received second operation of open reduction and plate fixation for the right fracture acetabular under general anesthesia, he had chest tightness, shortness of breath, PaO2 critical situation of declining. Orthopedic surgery was stopped and the rescue was implemented in the ICU ward immediately. ECG shows sinus tachycardia and S�Q� T� & V1rsr 'wave, which was believed to be acute pulmonary embolism. Lung perfusion ECT was done for the patient immediately in nuclear medicine department.

99mTc-MAA Lung perfusion Imaging showed lung with morphologic abnormalities. Right lung was lobe and segmental perfusion defects, and left lung shows segmental perfusion defects (figure 18). With normal X-ray before surgery (Nov. 18), V / Q diagnosis was doneacute pulmonary embolism. In the ICU ward the patient received anticoagulation and thrombolytic therapy. 2 weeks later (Dec. 4), pulmonary perfusion imaging (Figure 19) was reviewed, the original lobe and segmental perfusion defects had been seen the distribution of perfusion and lung morphology was normal after effectively treatment. X-ray and ECG were normal too. The patient was pulled through by accurate diagnoses and effective treatment.

Fig. 18. Lung perfusion imaging of post-traumatic acute pulmonary embolism

Medical Theory on Orthopedics Combining Molecular Imaging with Clinical Practice 89

[1] Jing jing Peng, Wei Tian \*(corresponding author) Application of bone scintigraphy in the

[2] Jing-jing Peng, Hong-hong Liu \*(corresponding author), Xia Fu-rong,Cai You-Bo 99mTc-

[3] Jing-jing Peng Advancement in application of *nuclear medicine* .China Contemporary

[4] Jing-jing Peng Advancement in clinical application of *orthopedic nuclear medicine*  (lectures)Chin J of Bone Tumor and Bone Disease 2009; 8(6): 356-359 [5] Jiang-lin Chen, Zhao-chang Lin, Shu-ping Tang.Case report: Qualitative and location

Medicine Apr.2006; 25 2:361-362 (PEER REVIEWS AND EVALUATIONS) [6] Book Orthopedic Nuclear Medicine, Berlin: springer, 2004 ISBN: 3-540-00614-1 Book

[7] Book *Diagnostic Imaging Orthopedic Nuclear Medicine* ISBN-978-7-117-13047-9/R·13048

[8] Book *Clinical Orthopedics* ISBN-7-5323-7404-1 Book Editor: Shu-huan Wang: Jing-jing

[9] Book Chinese *Medical Imaging* ISBN-978-7-117-12740-0/R·12741 Book Editor: Qian Zhou,

[10] Book *Practical Orthopedics of Jishuitan* ISBN-978-7-117-09461-0 Book Editor: Wei Tian

[11] Jing-jing Peng, Guo-wei Rong \* (corresponding author), Qing Zhang, You-bo Cai et,al

[12] Jin Feng, Jing-jing Peng \* (corresponding author), Hong-hong Liu Yang Fang, Xiao-hui

[13] Guo-wei Feng, Zhong-yi Yang, Liang Guan, Cheng-mo Zhu Case report: Lung

[14] Jing jing Peng, Xu Fu. Radionuclide Image manifestation characteristics in osteoarthritis

[15] Yan-xia Bai, Jing jing Peng \*(corresponding author), Fang Yang, Min-qiu Lu. Detecting

MDP Bone Imaging Diagnoses of parathyroid tumors. Chin J Nucl Med,

diagnosis with nuclear medicine of primary hyperparathyroidism. Anthology of

Editor:Abdelhamid. H. Elgazzar.(translation <Orthopedic Nuclear Medicine> into Chinese Publication ISBN-978-7-117-12367-9/R·12368 Book Editor:Jing-jing

Book Editor: Jing-jing Peng Chapter 1 Fundamental Researches: New concept of

Wanying Qu Jing-jing Peng Chapter Bone Scintigrapy: Primary bone tumors

Application of Radionuclide Imaging in Osteosarcoma. Chin J Nucl Med,

Niu Response of osteosarcoma to chemotherapy evaluated by 18F-FDG Imaging

Metastases Diagnosis with 99mTc-MDP Bone Scan Tracing of Osteosarcoma. (PEER REVIEWS AND EVALUATIONS) Chinese Journal of Nuclear Medicine

of knee Chin J Nucl Med, 1988;8(3):142-144 Chin J of Med Imaging Technology

bone lesions of patient multiple myloma on scintigraphy. Chin J Med Imaging

fracture diagnosis. Guide of China Medicine 2010; 8(5): 115-118.

**8. References** 

2003;23(6):263-265

Peng,Wei Tian \*)

section 4217-4221

2000;20(2):65-67

2007;(27)6:372

2008,24(1):127-130

Technol. 2008;24 (7):1106-1109

orthopedic molecular imaging

Peng Chapter: Radionuclide Imaging

Jing-jing Peng Chapter :PET Imaging 69-76

Chin J of Clinic med imaging 2010,21(9):638-640

Medicine 2001; 7(4):59-61

Fig. 19. 2 weeks after treatment, normal lung perfusion imaging

Timely diagnosis and successful treatment of the patient with large area of APE after injury is described in paper <Advancement in the Application of Nuclear Medicine> published in Apr.2001 V7N4:59-61 Journal of "China Contemporary Medicine". This paper inspired Beijing Ji Shui Tan Hospital on the understanding and study of acute pulmonary embolism[1. Doctors can see directly from the image: lower limb Thrombosis bring about post-traumatic pulmonary embolism is an important research topic. Early diagnosis and treatment for APE patients can prevent recurrent thromboembolism. It can improve the cure rate, reduce mortality and ensure medical safety of patients before and after surgery.

The development of molecular imaging in China should follow simple, efficient, accurate principles. Accuracy is the key]. Accurate diagnosis and effective treatment cost savings and improve quality of life. Development of medicine, science and technology reflects in significant health benefits for the people.

## **7. Acknowledgements**

The author would like to thank the teachers at JST Hospital Orthopedic: Prof. Shu-huan Wang, Prof. Guo-wei Rong, Beijing Hospital Nuclear Medicine -Prof. Wan-ying Qu and Peking Union Medical College Hospital -Prof. Qian Zhou for their valuable contribution and inspiration.

The author would also like to express gratitude to all who have kindly helped in realization of this chapter: JST Hospital lead orthopedist Wei Tian, oncologist You bo Cai, Qing-zhang, and pathologist Hong-hong Liu,surgeon Fu rong Xia,. Thank you for your expertise and scientific efforts. Thanks to the Technologists of Dept. Nuclear Medicine JST and my students Dr. Jin Feng, Dr. Lian-na Zhang and Dr. Fang Yang for their time and scrupulous work.The author would like to express her sincerest gratitude to the patients.

## **8. References**

88 Soft Tissue Tumors

Timely diagnosis and successful treatment of the patient with large area of APE after injury is described in paper <Advancement in the Application of Nuclear Medicine> published in Apr.2001 V7N4:59-61 Journal of "China Contemporary Medicine". This paper inspired Beijing Ji Shui Tan Hospital on the understanding and study of acute pulmonary embolism[1. Doctors can see directly from the image: lower limb Thrombosis bring about post-traumatic pulmonary embolism is an important research topic. Early diagnosis and treatment for APE patients can prevent recurrent thromboembolism. It can improve the cure rate, reduce mortality and ensure medical safety of patients before and after

The development of molecular imaging in China should follow simple, efficient, accurate

improve quality of life. Development of medicine, science and technology reflects in

The author would like to thank the teachers at JST Hospital Orthopedic: Prof. Shu-huan Wang, Prof. Guo-wei Rong, Beijing Hospital Nuclear Medicine -Prof. Wan-ying Qu and Peking Union Medical College Hospital -Prof. Qian Zhou for their valuable contribution and

The author would also like to express gratitude to all who have kindly helped in realization of this chapter: JST Hospital lead orthopedist Wei Tian, oncologist You bo Cai, Qing-zhang, and pathologist Hong-hong Liu,surgeon Fu rong Xia,. Thank you for your expertise and scientific efforts. Thanks to the Technologists of Dept. Nuclear Medicine JST and my students Dr. Jin Feng, Dr. Lian-na Zhang and Dr. Fang Yang for their time and scrupulous

work.The author would like to express her sincerest gratitude to the patients.

. Accurate diagnosis and effective treatment cost savings and

Fig. 19. 2 weeks after treatment, normal lung perfusion imaging

surgery.

inspiration.

principles. Accuracy is the key]

**7. Acknowledgements** 

significant health benefits for the people.


**5** 

*Japan* 

**Imaging Findings of Adipocytic Tumors** 

Adipose tissue tumors are the most common soft tissue tumors in both benign and malignant categories. A presumptive diagnosis of the adipose tissue tumors usually can be made based on the imaging findings [5]. However, there are some exceptions. Making differential diagnosis of hibernoma from lipoma-like well-differentiated liposarcoma may be difficult by imaging findings, while the making histological diagnosis is not difficult. Lipoma-like well-differentiated liposarcomas can mimic intramuscular or intermuscular lipomas in radiological as well as histological findings, and they may occasionally cause problems in establishing diagnosis and treatment planning. Although making differential diagnosis of these benign lesions from lipoma-like well-differentiated liposarcomas may be important, it may also be important to make a differential diagnosis between intramuscular lipoma, intermuscular lipoma and hibernoma for appropriate surgical treatment and follow-

The purpose of this section is to elucidate the differences in imaging features among these adipocytic neoplasms for appropriate treatment planning. The imaging findings of other

Intramuscular lipoma is difficult to differentiate from lipoma-like liposarcoma, and imaging findings are useful for differentiating from liposarcomas. The common sites of occurrence include the thigh (particularly the quadriceps and hamstring muscles), deltoid, triceps brachii and pectoralis major muscles.; all of which are relatively large muscles. The disease is most frequently found in the lower extremities, and is also commonly found in the upper extremities. As for the symptoms, a painless mass or tumor is the most common, accounting for approximately 60% of the cases [12], and a relatively large number of patients present mainly with swelling. A possible reason is that the lesions occur in the deep muscle layers and it cannot be easily palpated as a mass or tumor. Neuropathy is rarely seen: posterior interosseous nerve palsy is sometimes caused by the intramuscular lipoma in the supinator muscle. Pain as the main complaint is rare. CT findings are particularly characteristic. Typically, imaging features are spherical to oval, sharply demarcated space-occupying lesion whose density as a whole is the same as that of fat. The lesion has a streaky structure with the same density as that of the muscle (Fig. 1A). The thickness of the streaky structures

up, because differences in recurrence rates among these benign tumors exist.

**1. Introduction** 

adipocytic sarcomas are also included.

**2. Intramuscular lipoma** 

Jun Nishida, Shigeru Ehara and Tadashi Shimamura

*School of Medicine Iwate Medical University, Morioka City,* 

*Departments of Orthopaedic Surgery and Radiology,* 

[16] Zhang Yun-jian , Zhao Ning , Xia Guo-guang, Li Tian-shui, Wang Yan-xia. Prognostic factors for patients with pulmonary thromboembolism after orthopedic surgery Journal of Peking University (Health Sciences) 2010,42(6):798-710
