Bone marrow disorders: characterization with quantitative MR imaging

Thirty patients with various hematologic disorders and 15 healthy control subjects underwent quantitative magnetic resonance (MR) imaging of the lumbar spine with spin-echo techniques. Images of patients with infiltrative bone marrow disorders showed significantly more prolonged T1 times than those of control subjects (P less than .001). It was not possible to distinguish different diffuse infiltrative bone marrow disorders on the basis of T1 values. Aplastic anemia could be distinguished from normality because of significantly shortened T1 (P less than .001). A significant correlation was seen between T1 and bone marrow cellularity (r = .74, P less than .001). T2 was of no value in the characterization of bone marrow disorders. Quantitative MR imaging dose not improve the diagnostic potential of bone marrow imaging in the detection of diffuse marrow infiltrates.     

Structural and functional imaging of normal bone marrow and evaluation of its age-related changes

A number of noninvasive imaging techniques have been used for the evaluation of bone marrow, including magnetic resonance imaging (MRI) and bone marrow scintigraphy. The appearance of bone marrow on MRI varies considerably depending on the proportion of red and yellow marrow, and the composition of the red marrow and its distribution with relation to age and sex. The composition of bone marrow also can vary under physiological and pathological conditions. MRI is a highly sensitive technique for evaluating the bone marrow, but it is limited in its practical use for whole-body bone marrow screening. Bone marrow scintigraphy with radiolabeled compounds such as technetium-99m-labeled nanocolloid and monoclonal antibodies has the advantage of evaluating the entire bone marrow, and has been used for the diagnosis of various bone marrow disorders. In addition, (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging can be used to evaluate bone marrow metabolism and disease and to provide information about the state of the primary tumor, lymph nodes, and distant metastases. Understanding of the appearance of normal bone marrow, including age- and sex-specific differences with each of these imaging modalities, is essential to permit accurate diagnosis of benign and malignant bone marrow disorders. We present a review of MRI and scintigraphy of normal bone marrow with some emphasis on FDG-PET imaging in assessing marrow activity in normal and abnormal states and also present preliminary data regarding normal age-related changes in bone marrow through use of FDG-PET, as well as the role of segmentation of bone marrow on MRI for quantitative calculation of the metabolic volumetric product for red marrow metabolism using FDG-PET.     

Differential diagnosis of focal and diffuse neoplastic diseases of bone marrow in MRI

Magnetic resonance imaging (MRI) has become the preferred imaging modality for the evaluation of malignant disease in the bone marrow. Compared to bone marrow aspiration and biopsy, MRI is noninvasive and provides information by sampling a large volume of bone marrow. Due to disease-related alterations in the composition of bone marrow, MRI provides a very high sensitivity, but lacks specificity for most bone marrow disorders. However, MRI can be a very valuable diagnostic tool properly placed within the clinical context.     

Magnetic resonance of the bone marrow

Magnetic resonance imaging has opened new possibilities to current diagnostic radiology in the evaluation of bone marrow. In the past, bone marrow imaging was based on conventional radiology, nuclear medicine and computed tomography; they all exhibited some capabilities but also some limitations. Bone image on MR scans is due to bone marrow, with its different components of red and yellow marrow. Since red marrow is mostly liquid and yellow marrow contains large amounts of fat, the signal will vary, on T1-weighted images, according to their different proportions. There is a gradual change from red marrow to yellow marrow from birth to adulthood: this change determines the MR appearance of bone marrow, the different features of which should be known for a correct evaluation of pathologic findings. MRI is extremely effective in the evaluation of infiltrative disorders of bone marrow, such as leukemia, lymphoma, myeloma, primary and metastatic skeletal tumors, and infections. MRI allows depletive disorders of bone marrow and ischemic processes to be studied. Finally, MRI allows the non-invasive follow up of bone marrow pathologic conditions, thus representing a valid alternative to biopsy.     

Tc-99m HMPAO-labeled leukocytes for hematopoietic marrow imaging. Comparison with In-111 chloride.

The current study was initiated to define whether Tc-99m leukocyte imaging, compared to In-111 chloride imaging, could provide additional information on the hematopoietic activity of the bone marrow in diffuse hematologic disorders. A total of 11 patients with hematologic disorders were studied both with Tc-99m leukocytes and In-111 chloride. One patient with myelofibrosis showed disparate tracer distribution in the bone marrow between the two; Tc-99m leukocyte uptake in the central marrow was highly decreased, whereas In-111 chloride showed expanded marrow. The disparate results of granuloid hypoplasia and erythroid hyperplasia obtained by bone marrow biopsy and aspiration in this patient were thought to give an explanation for the radionuclide findings. The remaining 10 patients showed similar tracer distribution in the marrow, and the observation of hematopoietic cellularity confirmed by bone marrow biopsy and aspiration correlated well with the radionuclide findings. These results demonstrate that Tc-99m leukocytes may be a potential imaging agent for evaluating hematopoietic activity in the bone marrow, in particular granulopoietic activity.     

Recent advances in bone marrow scanning

Interest in bone marrow scanning has been renewed as the result of the development of radiopharmaceuticals for evaluating specific aspects of bone marrow anatomy, physiology and pathology. This article provides a brief review of bone marrow structure, blood flow and function essential to the understanding of basic principles of bone marrow radionuclide imaging. The prospects and limitations of imaging haematopoietic bone marrow in man using indium 111 chloride, technetium-99m (99mTc)-labelled microcolloid or 99mTc-labelled monoclonal antigranulocytic and antimyelocytic antibodies are discussed in more detail. The technical aspects of bone marrow scintigraphy are presented. Results of more recent studies evaluating bone marrow scanning in circulatory, inflammatory and in systemic haematological disorders are summarized. Special attention is paid to the concept of bone marrow micrometastases and its implications for the follow-up of patients with malignant tumours. Recent results suggest that immunoscintigraphy of bone marrow may provide a novel and sensitive approach for establishing the presence and extent of bone marrow infiltration.     

MR imaging of the foot and ankle: patterns of bone marrow signal abnormalities

Diagnosis of marrow disorders of the foot and ankle is among the more challenging aspects of MR interpretation. Evaluation of normal and abnormal bone marrow with regard to pattern, distribution, and signal characteristics on different sequences often allows a specific diagnosis. This pictorial review illustrates MR imaging findings of normal variants of bone marrow of the foot and ankle, and the varied responses of bone marrow to trauma, stress, or disease.     

Recent advances in bone marrow scanning

Interest in bone marrow scanning has been renewed as the result of the development of radiopharmaceuticals for evaluating specific aspects of bone marrow anatomy, physiology and pathology. This article provides a brief review of bone marrow structure, blood flow and function essential to the understanding of basic principles of bone marrow radionuclide imaging. The prospects and limitations of imaging haematopoietic bone marrow in man using indium 111 chloride, technetium-99m (^99mTc)-labelled microcolloid or^99mTc-labelled monoclonal antigranulocytic and antimyelocytic antibodies are discussed in more detail. The technical aspects of bone marrow scintigraphy are presented. Results of more recent studies evaluating bone marrow scanning in circulatory, inflammatory and in systemic haematological disorders are summarized. Special attention is paid to the concept of bone marrow micrometastases and its implications for the follow-up of patients with malignant tumours. Recent results suggest that immunoscintigraphy of bone marrow may provide a novel and sensitive approach for establishing the presence and extent of bone marrow infiltration.     

A technique for assessment of bone marrow composition using magnetic resonance phase interference at low field

In disorders which involve the bone marrow, the fat/water ratio of the marrow is often an indicator of the progress of disease. A noninvasive method of monitoring this ratio in bone marrow could be clinically useful. We have investigated a method of bone marrow assessment, using magnetic resonance imaging at low field (0.064 Tesla). The method has been tested using calibrated phantoms; we also present results from normal human subjects.     

Magnetic resonance imaging of bone marrow disorders

The sensitivity of MRI to marrow infiltration together with the ability to perform multiplanar imaging allows evaluation of the bone marrow in a manner that has never been feasible before. The clinical impact of this has yet to be fully realized. However, detection of focal marrow infiltration by MRI with concurrently normal conventional imaging studies has important clinical implications for staging and therapy. Proper staging of marrow-based neoplasms such as leukemia and lymphoma is fundamental to the determination of treatment and prognosis. MRI can be used to increase diagnostic certainty when a question exists concerning primary or metastatic marrow disease when other imaging studies are inconclusive. Chemical shift imaging may further improve the sensitivity and clinical utility of magnetic resonance imaging in patients with hematologic disorders involving the bone marrow.     

Musculoskeletal manifestations of chronic anemias

This article provides an overview of the current use of diagnostic imaging modalities in the evaluation of a heterogeneous group of disorders causing chronic anemias by impaired blood cell production (inherited bone marrow failure syndromes of childhood, aplastic anemia and myelodysplastic syndromes, β-thalassemia) or increased blood cell destruction (sickle cell disease). During the course of these disorders, various musculoskeletal abnormalities can be encountered, including marrow hyperplasia, reversion of yellow marrow to red marrow, growth disturbances, and, occasionally, extramedullary hematopoiesis. Diagnostic imaging may help the clinician to identify specific complications related to either the disease (e.g., bone infarction and acute osteomyelitis in sickle cell disease) or transfusion (e.g., iron overload due to increased hemolysis) and iron chelation (e.g., desferrioxamine-related dysplastic bone changes and deferiprone-related degenerative arthritis) treatments. In this field, magnetic resonance imaging plays a pivotal role because of its high tissue contrast that enables early assessment of bone marrow changes before they become apparent on plain films or computed tomography or metabolic changes occur on bone scintigraphy or positron emission tomography scan. Overall, familiarity with the range of radiological appearances in chronic anemias is important to diagnose complications and establish appropriate therapy.     

The role of MR imaging in scaphoid disorders

The scaphoid bone of the wrist is one of the most commonly fractured bones in the body. Due to its importance in the biomechanics and functionality of the wrist, it is important to depict and characterize the type of injury. Plain radiographs and scintigraphy may fail to disclose the type and severity of the injury. In patients with normal initial plain radiographs, MR imaging can discriminate occult fractures from bone bruises and may also demonstrate ligamentous disruption. MR imaging can also discriminate the proximal pole viability versus avascular necrosis secondary to previous fracture, which is important for treatment planning. Treatment of non-united fractures with vascularized grafts can be evaluated with contrast-enhanced MR imaging. Idiopathic osteonecrosis or Preiser’s disease was originally described after trauma. The non-traumatic disorders of the scaphoid include post-traumatic osteoarthritis, inflammatory bone marrow edema in patients with rheumatoid arthritis, and osteomyelitis. MR imaging is helpful in all the above disorders to demonstrate early bone marrow edema, cartilage degeneration and associated subchondral marrow changes. The most commonly found tumors in the scaphoid are usually benign and include enchondroma, osteoblastoma and osteoid osteoma. MR imaging is not mandatory for the initial diagnosis, which should be based on plain X-ray findings.     

Chemical shift imaging of bone marrow: preliminary experience

A phase-contrast method of chemical shift imaging was used to evaluate bone marrow in normal volunteers and in patients with metabolic, inflammatory, traumatic, and neoplastic disorders. Five normal volunteers were examined in order to obtain preliminary data on normal patterns of signal intensity in hematopoietic and fatty marrow using both conventional magnetic resonance imaging and proton chemical shift imaging. Normally, hematopoietic marrow yields low signal intensity on phase-contrast images; pathologic conditions affecting hematopoietic marrow typically result in increased signal intensity due to either accumulated lipid or water. Because of its high fat content, yellow marrow normally yields high signal intensity on phase-contrast images, whereas abnormal conditions usually result in decreased phase-contrast signal intensity due to increased tissue water. Proton chemical shift imaging is likely to be a valuable supplement to standard magnetic resonance imaging techniques in the study of bone marrow in vivo.     

Contrast-enhanced magnetic resonance imaging of bone marrow

In the assessment with magnetic resonance (MR) imaging of bone marrow disorders, the use of contrast agents is usually not critical because T1-weighted spin-echo and fat-suppressed sequences (STIR or fat-sat intermediate weighted) are robust and largely available techniques for depiction of neoplastic and non-neoplastic lesions of the bone marrow. This article discusses the characteristics of dynamic contrast-enhanced MR imaging of bone marrow edema, ischemia, and neoplasm. It emphasizes its value in staging and in monitoring of response to chemotherapy of several bone tumors. These fast dynamic contrast-enhanced techniques do not allow differentiation between benign and malignant primary osseous tumors because the biologic behavior rather than the malignant potential of these lesions is reflected.     

The evolving role of MRI in oncohaematological disorders

Magnetic resonance imaging (MRI) has opened new possibilities to current diagnostic radiology in the evaluation of bone marrow. Compared with other imaging modalities, MRI is the only technique able to directly visualise bone marrow with its different components of red and yellow marrow. Other advantages of MRI are high-contrast resolution and multiplanar view, as well as extensive coverage of the skeleton with whole-body MRI (WBMRI). However, specificity of signal alterations of bone marrow is low. Therefore, MRI findings need to be integrated with clinical and laboratory findings as well as with haematological and oncological evaluation. MRI provides information that effectively aids diagnosis, staging and follow-up of various bone marrow disorders. There is increasing interest in the capabilities of MRI in the evaluation of bone marrow, in particular of haematological malignancies. According to some authors much work remains to be done to improve sensitivity and specificity of MRI in order to define the real clinical value of this imaging modality in the multidisciplinary management of patients with a haematological malignancy. This article presents recent developments and perspectives in the use of MRI in oncohaematological diseases.     

18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment.

Few diagnostic procedures are available to determine the degree of bone marrow cellularity and the numbers of cycling cells in patients with bone marrow disorders. Noninvasive imaging of the bone marrow compartment may be helpful. The PET tracer 3'-fluoro-3'-deoxy-L-thymidine (18F-FLT) has been developed recently. 18F-FLT uptake is related to the rate of DNA synthesis and increases with higher proliferation rates in many types of cancer. Background uptake of 18F-FLT in bone marrow is common. 18F-FLT PET might, therefore, visualize the high cycling activity of hematopoietic cells in the bone marrow compartment. Therefore, we investigated the feasibility of visualization and quantification of the activity of the bone marrow compartment with 18F-FLT PET to distinguish different hematologic disorders. METHODS: Clinical and laboratory data of 18 patients with myelodysplasia (MDS), chronic myeloproliferative disorders, myelofibrosis, aplastic anemia, or multiple myeloma were correlated with the results of 18F-FLT PET using visual analysis and the standardized uptake value (SUV). Findings were compared with those of healthy control subjects (n = 14). RESULTS: With SUV and visual analysis, a distinction could be made between MDS (n = 9), chronic myeloproliferative disorders (n = 3), and myelofibrosis (n = 3) compared with healthy control subjects. A significant increase in 18F-FLT uptake was observed in all of the studied patients with MDS and myeloproliferative disorders. In contrast, patients with myelofibrosis and aplastic anemia (n = 1) demonstrated a decline in bone marrow 18F-FLT uptake compared with healthy control subjects. Comparable results were observed in osteolytic lesions of patients with multiple myeloma (n = 2). CONCLUSION: 18F-FLT PET can be used to visualize the proliferative activity of the bone marrow compartment and may be helpful to distinguish separate hematologic disorders.     

Acute bone marrow edema of the hip: role of MR imaging

Acute bone marrow edema of the hip is a diagnostic challenge for both radiologists and clinicians. Marrow edema is often seen in patients with hip pain and restriction of motion. In patients with acute non-traumatic hip pain, whose radiographs are negative or inconclusive, MR imaging is the imaging study of choice. MR imaging is the most sensitive and specific imaging technique for detecting transient osteoporosis and osteonecrosis, as well as for detecting and staging fractures and microfractures. MR imaging is able to show marrow involvement in various inflammatory disorders and to diagnose reactive marrow edema from femoroacetabular impingment and greater trochanteric pain syndrome. In patients with septic arthritis, it may also depict associated marrow edema and suggest its reactive or infectious origin. For the neoplastic disorders, although plain radiographs should be the initial examination, MR imaging may follow for assessing extension to the surrounding soft tissues and/or associated pathologic fracture, facilitating thus the treatment planning. Computed tomography is more accurate compared with MR imaging in diagnosing intra-articular osteoid osteomas.     

Relative roles of radionuclide scanning and radiographic imaging in eosinophilic granuloma

Twenty-four skeletal lesions were studied in seven patients with eosinophilic granuloma by radiographic skeletal surveys and radionuclide bone imaging. The radiographs detected 22 (92%) of these lesions and missed only two, whereas the scintiscans identified only 16 (67%) of these lesions, and missed eight. Radiographic skeletal survey and radionuclide bone imaging are complementary procedures in detecting bone lesions in bone marrow disorders, including eosinophilic granuloma. Use of either method alone is fraught with the danger of missing bone lesions of eosinophilic granuloma.     

Magnetic resonance imaging of the bone marrow in hematological malignancies

Despite its lack of specificity, magnetic resonance imaging (MRI) of the bone marrow has the potential to play a role in the management of patients with primary neoplastic disorders of the hematopoietic system, including lymphomas, leukemias and multiple myeloma. In addition to its use in the assessment of suspected spinal cord compression, bone marrow MRI could be used as a prognostic method or as a technique to assess the response to treatment. The current review addresses the common patterns of bone marrow involvement observed in primary neoplasms of the bone marrow, basic technical principles of bone marrow MRI, and several applications of MRI in selected clinical situations. Received 22 May 1997; Revision received 27 January 1998; Accepted 29 January 1998     

Radionuclide imaging of bone marrow disorders

Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as ^99mTc-nanocolloid, ^99mTc-sulphur colloid, ¹¹¹In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using ¹⁸F-FDG and ¹⁸F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed.