Musculoskeletal system

Diagnostic imaging has played a major role in the evaluation of patients with cancers of the bone and soft tissue. The imaging modalities have included radiography, computed tomography, magnetic resonance imaging, and bone scintigraphy. Current experience suggests that functional imaging with positron emission tomography (PET) and [F-18]fluorodeoxyglucose (FDG) may also have an important role in the imaging evaluation of patients with bone and soft tissue sarcoma, including guiding biopsy, detecting local recurrence in amputation stumps, detecting metastatic disease, predicting and monitoring response to therapy, and assessing for prognosis. Prospective studies with large patient groups will be essential to define the exact diagnostic role of FDG PET in this clinical setting, which should also include an evaluation of the cost-effectiveness and the short-term and long-term benefits in clinical decision making and management. In this article, we review the diagnostic utility of dedicated PET and PET combined with computed tomography imaging system in the evaluation of patients with bone and soft tissue malignancies.     

The reproductive tract

Diagnostic imaging has played a major role in the evaluation of patients with the cancers of the reproductive tract. The imaging modalities have included ultrasonography, computed tomography, magnetic resonance imaging, hysterosalpingography, and scintigraphy with radiolabeled monoclonal antibodies. Positron emission tomography (PET) with [F-18]fluorodeoxyglucose also has been shown to be useful in the imaging evaluation of these patients. Clinical applications have included initial staging and posttherapy restaging of disease, detecting metastatic disease, differentiating posttherapy anatomic alterations from recurrent or residual disease, and predicting and evaluating treatment response. In this article, we review the diagnostic utility of dedicated PET and combined PET-computed tomography systems in the imaging assessment of reproductive tract malignancies (excluding prostate cancer) in both sexes with an emphasis on fluorodeoxyglucose applications.     

Whole-body imaging of the musculoskeletal system: the value of MR imaging

In clinical practice various modalities are used for whole-body imaging of the musculoskeletal system, including radiography, bone scintigraphy, computed tomography, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). Multislice CT is far more sensitive than radiographs in the assessment of trabecular and cortical bone destruction and allows for evaluation of fracture risk. The introduction of combined PET-CT scanners has markedly increased diagnostic accuracy for the detection of skeletal metastases compared with PET alone. The unique soft-tissue contrast of MRI enables for precise assessment of bone marrow infiltration and adjacent soft tissue structures so that alterations within the bone marrow may be detected before osseous destruction becomes apparent in CT or metabolic changes occur on bone scintigraphy or PET scan. Improvements in hard- and software, including parallel image acquisition acceleration, have made high resolution whole-body MRI clinically feasible. Whole-body MRI has successfully been applied for bone marrow screening of metastasis and systemic primary bone malignancies, like multiple myeloma. Furthermore, it has recently been proposed for the assessment of systemic bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses) and muscle disease (e.g., muscle dystrophy). The following article gives an overview on state-of-the-art whole-body imaging of the musculoskeletal system and highlights present and potential future applications, especially in the field of whole-body MRI.     

Nuclear medicine in myeloma: the state of the science and emerging trends

We present the different imaging modalities in relation to myeloma, ranging from the time tested X-ray radiography to the newer promising methods of fluorine-18 fluorodesoxyglucose-positron emission tomography ((18)F-FDG-PET) and technetium-99m methoxy isobutyl isonitrite ((99m)Tc-MIBI) scintigraphy. A small discussion regarding newer methods such as fluoride-18 positron emission tomography ((18)F-PET), fluorine-18-fluoro-deoxy-L-thymidine positron emission tomography ((18)F-FLT PET), carbon-11 methionine positron emission tomography ((11)C-methionine PET) and the tritiated thymidine labeling index is also included. They have different mechanisms of tracer uptake enabling the visualization of the spectrum of the disease manifestations ranging from osteoblastic to osteolytic lesions, and also the study of the metabolic status, proliferative and protein activity, in skeletal and in extra-skeletal sites.     

The role of fluorodeoxyglucose, 18F-dihydroxyphenylalanine, 18F-choline, and 18F-fluoride in bone imaging with emphasis on prostate and breast

Diagnostic imaging has played a major role in the evaluation of patients with bone metastases. The imaging modalities have included bone scintigraphy, computed tomography, magnetic resonance imaging, and most recently PET/CT, which can be performed with different tracers, including fluorodeoxyglucose (FDG), 18F-fluoride, 18F-choline (FCH), and 18F-DOPA (dihydroxyphenylalanine). For most tumors the sensitivity of FDG in detecting bone metastases is similar to bone scintigraphy; additionally it can be used to monitor the response to chemotherapy and hormonal therapy. 18F-Fluoride may provide a more sensitive "conventional" bone scan and is superior for FDG nonavid tumors, but, nevertheless, FDG in "early disease" often has clear advantages over 18F-fluoride. Although more data need to be obtained, it appears that FCH is highly efficient in preoperative management regarding N and M staging of prostate cancer once metastatic disease is strongly suspected or documented. For neuroendocrine tumors and in particular in medullary thyroid cancer, DOPA is similar to 18F-fluoride in providing high quality information regarding the skeleton. Nevertheless, prospective studies with large patient groups will be essential to define the exact diagnostic role of FCH and DOPA PET in different clinical settings.     

SPECT/CT-Infektdiagnostik am Skelett

CLINICAL/METHODICAL ISSUE: Skeletal infections are often a diagnostic and clinical challenge. STANDARD RADIOLOGICAL METHODS: Nuclear imaging modalities used in the diagnostic workup of acute and chronic skeletal infections include three-phase bone scintigraphy and scintigraphy with labelled leucocytes. METHODICAL INNOVATIONS: The introduction of hybrid technologies, such as single photon emission computed tomography/computed tomography (SPECT/CT) has dramatically changed nuclear medical imaging of infections. PERFORMANCE: In general SPECT/CT leads to a considerably more accurate diagnosis than planar or SPECT imaging. ACHIEVEMENTS: Given the integrated acquisition of metabolic, functional and morphological information, SPECT/CT has increased in particular the specificity of three-phase skeletal scanning and scintigraphy with labeled leucocytes.     

Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer

Despite advances in morphological imaging, some patients with lung cancer are found to have non resectable disease at surgery or die of recurrence within a year of surgery. At present, metastatic bone involvement is usually assessed using bone scintigraphy, which has a high sensitivity but a poor specificity. We have attempted to evaluate the utility of the fluorine-18 deoxyglucose positron emission tomography (FDG PET) for the detection of bone metastasis. One hundred and ten consecutive patients with histological diagnosis of non-small cell lung cancer (NSCLC) who underwent both FDG PET and bone scintigraphy were selected for this review. In this group, there were 43 patients with metastatic disease (stage IV). Among these, 21 (19% of total group) had one or several bone metastases confirmed by biopsy (n = 8) or radiographic techniques (n = 13). Radionuclide bone scanning correctly identified 54 out of 89 cases without osseous involvement and 19 out of 21 osseous involvements. On the other hand, FDG PET correctly identified the absence of osseous involvement in 87 out of 89 patients and the presence of bone metastasis in 19 out of 21 patients. Thus using PET there were two false-negative and two false-positive cases. PET and bone scanning had, respectively, an accuracy of 96% and 66% in the evaluation of osseous involvement in patients with NSCLC. In conclusion, our data suggest that whole-body FDG PET may be useful in detecting bone metastases in patients with known NSCLC. Received 10 March and in revised form 7 May 1998     

FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy

The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewing's sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.     

FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy

The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewing's sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.     

The role of positron emission tomography in skeletal disease

The role of positron emission tomography (PET) in the evaluation and management of skeletal disorders is increasing. A number of reports are available in both benign and malignant disease with a variety of tracers. The bone agent 18F-fluoride can be used to evaluate bone metastases both qualitatively and, for a number of focal and systemic skeletal disorders, quantitatively. 18-Fluorodeoxyglucose is used as a tumor agent in both primary and metastatic bone and bone marrow malignancies; its use has also been described in the evaluation of infection within the skeleton. A possible role for the use of the hypoxia selective tracer 18F-fluoromisonidazole in skeletal infection also exists. This article summarizes the current role of PET in the skeleton with regard to these tracers and diseases.     

Detection of locoregional and distant recurrences in breast cancer patients by using FDG PET.

Cases of recurrence of breast cancer can pose considerable diagnostic and therapeutic challenges for the oncologic team. The prognosis and management decisions are based on knowledge of the true extent of disease. Conventional staging methods, including physical examination, assessment of levels of tumor markers, cross-sectional imaging, and bone scintigraphy, may not reliably demonstrate the extent of disease in all cases. Physical examination and cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging) can be problematic because (a) the sequelae of previous surgery and radiation therapy can be difficult to distinguish from recurrent neoplasms and (b) early metastatic disease (small lesions) can be difficult to distinguish from benign lesions that are too small to characterize. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) can help clarify inconclusive findings from physical examination and cross-sectional imaging. FDG PET is more sensitive than CT in detection of lymphatic spread of disease to locoregional and mediastinal nodes. Metastases at distant sites including the lung, bone, and the liver are also readily detected at FDG PET. FDG PET has been proved accurate in restaging cases of recurrent breast cancer and will likely aid in directing therapy in these cases.     

PET/CT in malignant bone disease

The most commonly used positron emission tomography (PET) tracer in clinical practice, fluorine-18 fluorodeoxyglucose ( (18)F-FDG) is a glucose analogue that directly gains entry in excess into tumor cells. It is therefore sensitive for the detection of early bone marrow involvement prior to any identifiable bone changes. The introduction of (18)F-FDG-PET in the imaging algorithms of various malignant diseases often obviates the need to perform a separate assessment of malignant bone involvement with conventional bone scintigraphy. After therapy, disappearance of (18)F-FDG accumulation indicates success even when the bone remains morphologically abnormal. Novel hybrid systems composed of PET and computed tomography (CT) allow for acquisition of both modalities in the same clinical setting and the generation of fused functional-anatomical images. This technique has been found to improve the diagnostic accuracy of PET in detecting malignant bone involvement. This article discusses the role of PET/CT, primarily (18)F-FDG PET/CT, in the assessment of malignant bone involvement in patients with primary bone sarcomas, common solid malignancies, lymphoma, and multiple myeloma.     

The role of single-photon emission computed tomography/computed tomography in benign and malignant bone disease

Radiological (plain radiographs, computed tomography [CT], magnetic resonance imaging [MRI]) and nuclear medicine methods (bone scan, leukocyte scan) both provide unique information about the status of the skeleton. Both have typical strengths and weaknesses, which often lead to the sequential use of different procedures in daily routine. This use causes the unnecessary loss of time and sometimes money, if redundant information is obtained without establishing a final diagnosis. Recently, new devices for hybrid imaging (single-photon emission computed tomography/computed tomography [SPECT/CT], positron emission tomography/computed tomography [PET/CT]) were introduced, which allow for direct fusion of morphological (CT) and functional (SPECT, PET) data sets. With regard to skeletal abnormalities, this approach appears to be extremely useful because it combines the advantages of both techniques (high-resolution imaging of bone morphology and high sensitivity imaging of bone metabolism). By the accurate correlation of both, a new quality of bone imaging has now become accessible. Although researchers undertaking the initial studies exclusively used low-dose CT equipment, a new generation of SPECT/CT devices has emerged recently. By integrating high-resolution spiral CT, quality of bone imaging may improve once more. Ongoing prospective studies will have to show whether completely new diagnostic algorithms will come up for classification of bone disease as a consequence of this development. Besides, the role of ultrasonography and MRI for bone and soft-tissue imaging also will have to be re-evaluated. Looking at the final aim of all imaging techniques--to achieve correct diagnosis in a fast, noninvasive, comprehensive, and inexpensive way--we are now on the edge of a new era of multimodality imaging that will probably change the paths and structure of medicine in many ways. Presently, hybrid imaging using SPECT/CT has been proven to increase sensitivity and specificity of bone scintigraphy. This was mainly achieved by identifying benign bone conditions with increased bone turnover. Therefore, SPECT/CT should be applied whenever equivocal findings of planar bone imaging occur. It also helps to improve accuracy of leukocyte scanning to detect/exclude osteomyelitis and to define sites of inflammation. We therefore regard SPECT/CT as a valuable tool to optimize bone imaging, which might become even more important if new radiopharmaceuticals become available to image specific cell functions.     

Nuclear medicine of bone

Bone scintigraphy using 99mTc-labeled phosphorous compounds was found to be the most frequently ordered nuclear medicine examination in a nationwide survey in Japan, and has been used for the detection of lesions and the evaluation of disease progression and response to therapy in various skeletal diseases. In this article, we review improvement of the diagnostic sensitivity and specificity for bone metastasis of not only nuclear medicine techniques, such as planar imaging, SPECT, early flow phase imaging and quantification of bone scintigraphy, and bone marrow scintigraphy but also such recently developed methods as bone mineral measurement, and bone metabolic marker assays. In addition, radionuclide therapy of intractable bone pain due to bone metastasis is also addressed.     

Detection of multiple myeloma by PET/CT in a patient with colon cancer

A 76-year-old man with previous sigmoid colon resection for adenocarcinoma had low back pain for 2 months. Whole-body bone scintigraphy showed multiple focal Tc-99m methylene diphosphonate (MDP)-avid lesions in both rib cages and 3 lumbar vertebrae, indicating metastases. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging was performed for further evaluation of this possible metastatic disease and demonstrated the lumbar and costal metastases and several hypermetabolic areas in the pelvic bones, multiple thoracic vertebrae, both shoulders, and the right femur. Histopathologic examination of the right-sided iliac crest, however, revealed multiple myeloma.     

Pediatrics: diagnosis of neuroblastoma

Neuroblastoma is the most common pediatric extracranial soft-tissue tumor, accounting for approximately 8% of childhood malignancies. Its prognosis is widely variable, ranging from spontaneous regression to fatal disease despite multimodality therapy. Multiple imaging and clinical tests are needed to accurately assess patient risk with risk groups based on disease stage, patient age, and biological tumor factors. Approximately 60% of patients with neuroblastoma have metastatic disease, most commonly involving bone marrow or cortical bone. Metaiodobenzylguanidine (mIBG) scintigraphy plays an important role in the assessment of neuroblastoma, allowing whole-body disease assessment. mIBG is used to define extent of disease at diagnosis, assess disease response during therapy, and detect residual and recurrent disease during follow-up. mIBG is highly sensitive and specific for neuroblastoma, concentrating in >90% of tumors. mIBG was initially labeled with (131)I, but (123)I-mIBG yields higher quality images at a lower patient radiation dose. (123)I-mIBG (AdreView; GE Healthcare, Arlington Heights, IL) was approved for clinical use in children by the Food and Drug Administration in 2008 and is now commercially available throughout the United States. The use of single-photon emission computed tomography and single-photon emission computed tomography/computed tomography in (123)I-mIBG imaging has improved certainty of lesion detection and localization. Fluorodeoxyglucose positron-emission tomography has recently been compared with mIBG and found to be most useful in neuroblastomas which fail to or weakly accumulate mIBG.     

Two more cases of evaluation of POEMS syndrome using 18-FDG PET/CT

Following the article of Alberti et al., we would like to provide our own experience with two more cases in evaluation of POEMS syndrome using morphological and functional imaging modalities, including plain X-rays, computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy and positrons emission tomography with computed tomography (PET/CT). Among them, 18-FDG PET/CT proved its usefulness allowing extensive screening of the bony lesions involved.     

Bone scan update

The radionuclide bone scan is one of the most commonly performed pediatric nuclear medicine procedures. Bone scintigraphy is used as the diagnostic procedure of choice for diagnosis of bone and soft-tissue infection and can aid in the diagnosis of occult trauma without radiographic findings. There is a complimentary role for bone scintigraphy in the assessment of a child with suspected nonaccidental injury. The use of bone scan in a child with unexplained bone pain or limp may provide a diagnosis that could be related to trauma, tumor, or inflammation. A negative bone scan can help relieve concern for significant pathology. Bone scans in children require careful attention to technique to obtain high-quality diagnostic images. Routine whole-body imaging, magnification, additional views, and the use of single-photon emission computed tomography also are a routine part of this examination in children. Correlation with conventional radiographs is mandatory, and the judicious use of hybrid imaging with the addition of computed tomography may further improve diagnostic acumen, confidence and accuracy. New radiopharmaceuticals such as fluorine-18 may also play a role in changing techniques for pediatric bone scintigraphy.     

Internal derangement of the temporomandibular joint: detection by single-photon emission computed tomography. Work in progress

The diagnostic accuracy of both planar and single-photon emission computed tomography (SPECT) bone scintigraphy, radionuclide angiography, arthrography, and conventional radiography was evaluated in 36 patients with temporomandibular joint (TMJ) dysfunction undergoing preoperative testing. The sensitivity of SPECT bone scintigraphy (0.94) was comparable with arthrography (0.96) and significantly better than planar bone scintigraphy (0.76), radionuclide angiography (0.35), and transcranial lateral radiographs (0.04). While data for a larger asymptomatic control population are needed, preliminary results give SPECT a diagnostic specificity of 0.70 for internal derangements of the TMJ requiring surgical correction. It is concluded that SPECT bone scintigraphy is a useful noninvasive imaging test to screen for internal derangement of the TMJ.     

Fluorine-18-deoxyglucose-positron emission tomography imaging with magnetic resonance and computed tomographic correlation in the evaluation of bone and soft-tissue sarcomas: a pictorial essay

Positron emission tomography (PET) imaging has a growing role as an imaging modality to be used in conjunction with magnetic resonance and computed tomographic imaging in the detection, staging, and management of many sarcomas and carcinomas. Since PET is a relatively new modality and the incidence of sarcomas is low, it has not yet been approved for use in all bone and soft-tissue sarcomas. The purpose of this article is to pictorially evaluate soft-tissue and bone sarcomas, including malignant peripheral nerve sheath tumor, synovial sarcoma, osteosarcoma, liposarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma, fibrosarcoma, and myxofibrosarcoma. This pictorial essay illustrates and describes these tumors in various stages of disease progression vis-à-vis fluorine-18-deoxyglucose-PET imaging with computed tomographic and magnetic resonance correlation. Various stages of disease progression will be discussed including initial diagnosis, treatment response, and metastatic involvement.