The role of MRI in the assessment of bone marrow

The role of MRI in the assessment of bone marrow Poster No.: C-2180 Congress: ECR 2010 Type: Topic: Educational Exhibit Musculoskeletal Authors: J. Acosta Batlle, S. Hernandez Muñiz, B. Palomino Aguado, D. López Parra, I. Alba de Caceres, J. Albillos Merino; Madrid/ES Keywords: DOI: bone marrow infiltration, bone marrow and MRI, bone marrow replacement 10.1594/ecr2010/C-2180 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 13

Learning objectives To describe the normal and abnormal imaging features of bone marrow using magnetic resonance imaging (MRI), showing illustrative examples. Background Hematopoietic (red) marrow is present throughout the entire skeleton at birth, but over the ensuing two decades of life different regions of hematopoietic marrow convert to fatty (yellow) marrow. This conversion begins in the periphery of the skeleton and then symmetrically extends into the central skeleton. An additional, superimposed sequence of marrow conversion occurs in the long bones, starting in the diaphyses and progressing towards the metaphysis (particularly the distal metaphysis) (Fig. 1) on page. In the second decade of life, marrow in the long bones becomes predominantly fatty, except in the proximal metaphyses. In the late third decade, the marrow distribution reaches its mature state, with red marrow occupying the cranial vault, the spine, the ribs, the sternum, the clavicles, the scapulae, the pelvic region, and the proximal metaphyses of the femur and humerus; later in life even those regions gradually convert to yellow marrow. At times of sustained demand for increased hematopoiesis (chronic infection, anemia, heavy smoking, obesity, middle age in women, long-distance running), yellow marrow can reconvert to red marrow. Reconversion occurs in the reverse sequence from that of normal developmental conversion. It is faster in flat bones (sternum, spine, scapula). Red marrow contains about 50% of fat cells and 50% of hematopoietic cells embedded in a network of highly permeable sinusoids. Yellow marrow almost exclusively contains fat cells and few capillaries. Imaging findings OR Procedure details Bone marrow is composed predominantly of fat and water, the relative proportions of which affect the signal intensity of marrow at MRI (Fig. 2) on page. Page 2 of 13

1. MRI TECHNIQUES 1a. T1-Weighted Spin-Echo Sequence The T1-weighted (W) spin-echo (SE) sequence is the most important sequence for bone marrow MRI. The signal intensity of yellow marrow is similar to that of subcutaneous fat in T1-W SE images, whereas the signal intensity of red marrow is lower than that of subcutaneous fat, but higher than that of normal muscle and the intervertebral disc. Marrow lesions, whether benign or malignant, manifest similar or lower signal intensity than muscle on T1-W SE images, which contrasts with the surrounding high-signalintensity yellow marrow. One should always keep in mind that even a normal looking T1-W SE image of the marrow does not enable one to exclude marrow infiltration by abnormal cells because a certain level of infiltration must be reached before the water/fat balance becomes sufficiently altered. 1b. Intermediate-Weighted Spin-Echo Sequence The intermediate-weighted Spin-Echo sequence without fat saturation has no role to play in marrow imaging. 1c. T2-Weighted Fast Spin-Echo Sequence The T2-W fast SE sequence has a limited value for lesion detection but can contribute to lesion characterization. 1d. Fat-Saturated Spin-Echo Sequences Fat saturation plays an important role in bone marrow imaging. The use of a fat-suppression option is essential when obtaining T2-W fast SE sequence, as both fatty marrow and tumours have similar, moderately high signal intensity on that sequence. Page 3 of 13

1e. STIR Sequence The STIR sequence, in which the inversion time is selected to suppress fat contribution, provides valuable information because the signal of fat is suppressed and T1 and T2 contrast are added. It is highly sensitive in demonstrating marrow lesions and it is also less affected by magnetic-field inhomogeneities than is the fat-suppression option. 1f. Opposed-phase Chemical-shift Imaging A gradient-echo pulse sequence with an appropriate echo time, shows loss of signal in all normal marrow due to the presence of both lipid and water in marrow-containing voxels (Fig. 3 on page ). Tumour replaces normal marrow and does not contain lipid; therefore, tumour will not show signal loss on opposed-phase images. In fact, demonstration of fat within a bone lesion effectively excludes the presence of tumour. 1g. Gadolinium-Enhanced Sequences Normal marrow enhances on dynamic MRI after injection of gadolinium-dtpa, but is slower at routine T1-W SE MRI. Strong marrow enhancement occurs in a variety of processes, such as infection, inflammation, and tumour, limiting the role of enhancement in differentiating these phenomena. 1h. Diffusion-Weighted imaging Diffusion MRI measures the mobility of the water protons in a tissue and thus provides a window to tissue microstructure. Tumor and infection restrict the free diffusion of water molecules, and appear hyperintense at DWI. Benign edema and necrosis post-qt do not restrict the free diffusion of water molecules. However, reports on the utility of diffusion-weighted imaging (DWI) in marrow imaging have reached contradictory conclusions. Some stated that malignant spinal compression fractures are hyperintense to normal marrow and benign (mostly osteoporotic) compression fractures are hypointense at DWI, whereas others found no substantial discriminatory findings at DWI. A recent meta-analysis concluded that the mean apparent diffusion coefficient (ADC) values obtained at DWI are significantly higher in benign spinal fractures than in malignant ones and hypointense lesions at DWI are more likely to be benign (Fig. 4) on page. Page 4 of 13

2. MRI NORMAL ANATOMY Normal hematopoietic (red) marrow shows intermediate signal intensity on both T1- and T2-weighted (W) spin-echo (SE) images, whereas the signal intensity of fatty (yellow) marrow is similar to that of subcutaneous fat. On T1-W SE images, signal intensity of normal lumbar vertebral bodies should be higher than that of adjacent intervertebral disc or paravertebral muscles in an adult patient. In the thoracic spine, marrow signal intensity can be lower than that of discs. In the pelvis, normal marrow signal intensity should be higher than that of adjacent normal muscles. After intravenous injection of gadolinium-containing contrast material, enhancement of marrow signal intensity is barely visible at visual inspection on T1-W SE images. Performing dynamic MR studies can quantitatively assess signal enhancement. Usually, normal marrow signal intensity should not increase by more than 35% in adults older than 35 years of age. In normal fatty marrow, contrast-induced alteration of signal intensity is not visible (Fig 5) on page. On STIR, fat-saturated T2- or intermediate-w fast SE images, vertebral red marrow signal intensity normally ranges from intermediate to moderately elevated (Fig. 6) on page. 3. MRI NORMAL VARIANTS 3a. Islands of Hematopoietic Marrow Random variations in red marrow cellularity occur and cause the presence of areas of more pronounced decrease in signal intensity than adjacent marrow on T1-W SE images. The margins of these nodules are sharp if the marrow conversion process is advanced and fuzzier if the marrow conversion process is limited. Occasionally, central areas of high signal intensity are present on T1-W images due to the persistence of fat cells, and these are an additional argument in favour of a normal variant (Fig. 7) on page. 3b. Hematopoietic Marrow Hyperplasia Diffuse hematopoietic marrow hyperplasia is defined by the presence of hypercellular hematopoietic marrow in the axial skeleton and by expansion of hematopoietic marrow in Page 5 of 13

the appendicular skeleton (marrow reconversion). It can be idiopathic, mainly in middleaged obese woman. It also occurs in heavy smokers and in subjects with intensive sports activities. It is similar to what occurs in patients in response to stimuli that trigger the production of red marrow cells, including administration of hematopoietic growth factors during chemotherapy, chronic infection, and any other cause of chronic anemia, such as hereditary hemoglobinopathies. On T1-w SE images, hematopoietic marrow hyperplasia is associated with a marked decrease in signal intensity of vertebral marrow that becomes lower than that of adjacent disc or muscles (Fig. 8) on page, (Fig. 9) on page, (Fig. 10) on page. Marrow signal intensity is low on T2-w SE images. After intravenous gadolinium injection, signal intensity enhancement is moderate but can increase up to 80% on dynamic T1- w SE images. Differentiation of hematopoietic marrow hyperplasia from diffuse marrow infiltration remains extremely difficult, and blind iliac crest biopsy could be the most accurate technique to definitely address this occasionally difficult problem. 3c. Islands of Fatty Marrow During adulthood, foci of yellow marrow appear in the vertebral bodies. Their signal intensity is high on T1-W SE images and low on fat-sat images. On T2-W fast SE images, they also show high signal intensity and they should not be confused with clinically significant marrow lesions (Fig. 11) on page. 3d. Vertebral Hemangioma On T1-W images, its signal is generally higher than that of adjacent marrow, although it can also be equivalent and therefore not visible on T1-W images. On T2-W SE images, its signal is consistently high (Fig. 12) on page. Punctuated or linear areas of low signal intensity are also seen on T1- and T2-W images. Signal enhancement of hemangioma after gadolinium injection is variable. 3d. Enostosis or Compact Bone Island Its signal intensity is very low on all sequences, its contours are speculated, and adjacent marrow generally has a normal appearance. Page 6 of 13

4. MRI PATTERNS OF MARROW LESIONS Bone marrow lesions can be classified into a small number of lesion categories based on their signal intensity on T1-W SE images. These patterns are generally non-specific and can be observed within the same lesion. 4a. Marrow Depletion Marrow depletion is a pattern characterized on T1-W images by an increase in signal intensity in comparison with adjacent red marrow. Focal hematopoietic marrow depletion occurs in the spine of normal subjects, with increased frequency according to age. It also occurs in bone lesions, including quiescent lesions, Paget's disease, and vertebral hemangioma. Regional hematopoietic marrow depletion occurs after radiation therapy. Diffuse hematopoietic marrow depletion can be induced by drugs, and in aplastic anemia. 4b. Marrow Infiltration Marrow infiltration is a pattern characterized by a subtle to moderate decrease in marrow signal intensity on T1-W SE images. Margins are generally indistinct with a zone of gradual transition toward normal bone marrow. The term infiltration suggests that the abnormal marrow component infiltrates or permeates the normal marrow constituents with some possible residual adipocytes. Focal marrow infiltration involves the periphery of many abnormal processes including fracture, tumor, infection and osteoarthritis. Diffuse marrow infiltration occurs in systemic disorders including anemia, chronic infection, the acquired immunodeficiency syndrome (AIDS) (Fig. 13A) on page, (Fig. 13B) on page, and bone marrow cancers. The term bone marrow edema is frequently used to describe marrow infiltration with high signal intensity on T2-W SE images and a return to normal signal intensity on gadoliniumenhanced T1-W images. 4c. Marrow Replacement Page 7 of 13

Marrow replacement is a pattern characterized by a marked decrease in signal intensity on T1-W SE images. The term replacement suggests that normal marrow components are completely replaced by abnormal marrow components without residual adipocytes. Margins can be either sharp or indistinct depending on the absence or presence of surrounding marrow infiltration. Marrow replacement can be diffuse or focal. 5. NEOPLASTIC DISORDERS Determining the number of lesions has important implications. Benign lesions tend to involve multiple sites, as in polyostotic fibrous dysplasia, enchondromatosis, multiple osteocartilaginous exostoses, Langerhans cell histiocytosis, hemangiomatosis (Fig. 14A) on page, (Fig. 14B) on page, and fibromatosis. In contrast, primary malignancies, such osteosarcoma, Ewing sarcoma, fibrosarcoma, and malignant fibrous histiocytoma, rarely present as multifocal disease. Multiple malignant lesions usually indicate metastatic disease, multiple myeloma, or lymphoma. 5a. Leukemia Leukemic infiltration of bone marrow generally manifests as diffusely decreased marrow signal on T1-W images, although the marrow signal may appear normal in the presence of only minimal infiltration (Fig. 15) on page. 5b. Multiple Myeloma On T1-W images, multiple myeloma typically manifests as either a variegated pattern of small hypointense lesions throughout the bone marrow (Fig. 16) on page ; larger, focal bone marrow lesions; or diffusely low bone marrow signal. Like most tumours, leukemia and multiple myeloma show high signal on T2-W images and enhance more than red marrow after administration of gadolinium-based contrast material. In patients with multiple myeloma, spinal compression fractures can be due to underlying generalized osteopenia or to destructive bony changes from gross tumour deposits. Of note, a new spinal compression fracture occurring during treatment of multiple myeloma may be the result of successful tumour lysis, since, once the solid tumour mass has been destroyed, the remaining, weakened bone is no longer able to fulfil its biomechanical supporting role and thus collapses. Page 8 of 13

The new Dure/Salmon PLUS system for initial staging of multiple myeloma incorporates whole-body positron emission tomography (PET)/computed tomography (CT) or MRI of the spine and pelvis, rather than relying on the traditional radiographic skeletal evaluation to assess the tumour burden in the bone marrow (Fig. 17) on page. The number of bone marrow lesions shown at MRI correlates with both treatment outcome and overall survival. However, lesions may persist at MRI for 9-12 months after successful treatment follow-up. PET/CT is helpful in this situation, as active myeloma is fluorodeoxyglucose (FDG)-positive, whereas FDG uptake decreases rapidly after effective treatment. 5c. Lymphoma Lymphoma deposits in bone marrow are usually focal or diffuse, showing signals similar to those of other tumours. In cases of multifocal lymphoma, MRI can be useful for demonstrating sites of marrow involvement and provides an alternative to relying solely on the results of routine biopsy of the posterior iliac crests to assess the bone marrow (Fig. 18) on page, (Fig 19) on page, (Fig. 20A) on page, (Fig. 20B) on page. 5d. Metastases (Fig. 21) on page Metastatic lesions usually are low in T1-weighted signal intensity, lower, in fact, than adjacent muscle or a normal intervertebral disc. They are often higher in signal intensity than adjacent marrow on T2-weighted sequences because of high cellular content and adjacent edema, which can be extensive. On fat-suppressed T2-W images, most metastases -especially lytic and mixed- show increased signal throughout or in a peripheral rim (Fig. 22) on page, (Fig. 23) on page, (Fig. 24) on page, (Fig.25) on page. Some tumours, such as myxoid liposarcoma, have a propensity to metastasize to bone marrow without producing abnormalities on radiographs, CT, or bone scans. The presence of bone marrow edema that extends far beyond the margins of a bone lesion has been shown to favour a benign etiology for the lesion. Extensive edema has been reported in association with osteoid osteoma, osteoblastoma, chondroblastoma, Langerhans cell histiocytosis, and solid aneurismal bone cyst, as well as in osteomyelitis. Distinguishing between benign and malignant vertebral fractures at imaging can be challenging, and clinical information may not be revealing (Fig. 26) on page. Page 9 of 13

Features suggestive of a malignant spinal fracture are: involvement of an entire vertebral body, inhomogeneous enhancement of the vertebra, extension of signal abnormality into the pedicles, a convex contour of the collapsed vertebral body, the presence of an associated epidural mass, and a cervical or lumbosacral location of the collapsed vertebra (Fig. 27) on page. Features suggestive of a benign spinal fracture are: presence of a retropulsed bone fragment, preservation of fatty marrow throughout the vertebra, lack of high signal on T2-W images, only a small amount of soft tissue associated with the fracture, and the presence of a horizontal fracture plane evident on post-gadolinium images (Fig. 28) on page, (Fig. 29) on page. 6 NON-NEOPLASTIC DISORDERS 6a. Bone Marrow Edema Syndrome The clinical entity referred to as bone marrow edema (BME) syndrome is characterized by a painful joint associated with a pattern of bone marrow edema on MRI. BME shows low signal intensity on T1-W images, high signal intensity on T2-W and Stir images, and enhancement after paramagnetic contrast administration. Clinical disorders presenting with the common imaging finding of BME pattern include the transient osteoporosis or transient bone marrow edema syndrome (Fig. 30) on page, regional migratory osteoporosis, and reflex sympathetic dystrophy. 6b. Osteonecrosis Osteonecrosis (ON) usually involves adults in their third to fifth decades of life. Males and females are almost equally affected in most series. In 80% of patients with osteonecrosis, predisposing factors, such as administration of steroids, excessive alcohol consumption, sickle-cell disease, lupus erythematosus, or renal transplantation, can be identified (Fig. 31) on page, (Fig. 32) on page, (Fig. 33) on page. Many studies have shown that patients with ON of the femoral head lack typical findings of BME in the early stages of the disease, and that BME is never found before the appearance of band patterns at MRI. Indeed, the band pattern is the initial MRI finding of early ON. Studies have shown that BME developed after the onset of hip pain and correlated significantly with the subsequent collapse of the femoral head, suggesting progression to advanced ON (Fig. 34) on page. In addition, BME in ON correlates highly with necrotic volume and worsening of hip pain, thus representing a poor prognostic sign of the disease. Page 10 of 13

6c. Bone Bruise A bone bruise represents marrow edema and hemorrhage resulting from disrupted trabeculae following a single traumatic event (Fig. 35) on page. The pattern of bone bruise may suggest the mechanism of injury and, thus, the structures that might be involved. A bone bruise is commonly associated with chondral and osteochondral injuries, particularly in the growing skeleton. The term "fracture" is employed only when the overlying cortex is disrupted. Bone bruises resolve within 6-12 weeks, in parallel with clinical improvement. 6d. Stress-related Bone Injuries The persistent overuse of bone that is not yet accustomed to new or frequently applied forces results in microscopic trabecular fractures called stress response. This is the most benign event in the spectrum of stress injuries and indeed represents a physiological attempt to balance normal and maladaptive remodelling. In most such cases, MRI demonstrates BME without a fracture line. Failure of the patient to rest and allow the bone to heal results in a fatigue fracture, which is usually occult in early radiographs but quite obvious on MRI, which shows a low signal intensity fracture line and surrounding BME. Insufficiency fractures (IF) occur when normal muscular activity is applied to a bone that is deficient in mineral and/or elastic resistance. IF may be seen in healthy women with recent gestation and prolonged lactation, as well as in elderly postmenopausal women and patients with osteopenia due to steroid administration or to metabolic or endocrine disorders. By definition, IF occur either spontaneously or after minimal trauma. Early radiographs may be normal. MRI demonstrates extensive BME surrounding a low signal intensity fracture line (Fig. 36) on page. 6e. Reactive Bone Marrow Edema Infectious arthritis, rheumatoid arthritis, gout, and osteomyelitis should be distinguished from BME since they may present with reactive BME. Clinical history and physical examination may reveal predisposing conditions and associated systemic symptoms. The associated articular findings at MRI and the results of routine laboratory examinations are also helpful (Fig 37) on page, (Fig 38) on page, (Fig 39) on page. 6f. Storage Diseases Page 11 of 13

Various storage diseases are associated with bone marrow involvement. Gaucher disease is the most prevalent lysosomal storage disorder, leading to deposition of glycocerebrosidase-loaded macrophages in the marrow. MRI is useful for elucidating the underlying cause of bone pain, which these patients commonly present. In addition, MRI is able to assess quantitatively the degree of marrow replacement and thus to monitor the response to treatment. Conclusion Bone marrow is a functional tissue that changes its composition through life. MRI is a useful tool for differentiating between benign and malignant processes of bone marrow. MRI is capable of detecting bone marrow abnormalities in patients with haematological malignancies or other oncologic disease, as well as monitorizing treatment response and helping to determinate prognosis. Personal Information jacostabatlle@yahoo.es References 1. Alyas F, Saifuddin A, Connell D. MR imaging evaluation of the bone marrow and marrow infiltrative disorders of the lumbar spine. Magnetic Resonance Imaging Clinics of North America 2007. 15(2); 199-220. 2. Bredella MA, Stoller DW. Marrow imaging. Magnetic Resonance Imaging in Orthopaedics and Sports Medicine. Lippincott Williams and Wilkins 2007. Vol two. Pag 1977-2044. 3. Hwang S, Panicek DM. Magnetic resonance imaging of bone marrow in oncology, Part 1. Skeletal Radiol 2007. 36:913-920. Page 12 of 13

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