Review

Sclerotic Lesions of the Spine: MRI Assessment

Charles Mugera, MD1, Kyung J. Suh, MD, PhD2, Thierry A.G.M. Huisman, MD1,

Kristi Weber, MD1, Allan J. Belzberg, MD1, John A. Carrino, MD, MPH1, and

Avneesh Chhabra, MD1*

Sclerotic (T2 dark) lesions of the spine are infrequent and,as a result, these are often missed or misdiagnosed. Plainfilms may not be always available during magnetic reso-nance imaging (MRI) readout. Knowledge of such lesionsand their imaging appearances on MRI evaluation isessential for a reader. Additionally, a systematic approachis important to accurately diagnose these lesions. In thisarticle we discuss the various causes of spinal scleroticlesions, describe their MRI characteristics with relevantcase examples, and outline a systematic approach to theirevaluation.

Keywords: sclerotic lesions; spine; focal; diffuse

J. Magn. Reson. Imaging 2013;38:1310–1324.VC 2013 Wiley Periodicals, Inc.

SCLEROTIC (T2 dark) lesions of the spine are infre-quent and, as a result, these are often missed or mis-diagnosed (1,2). Plain films may not be alwaysavailable during magnetic resonance imaging (MRI)readout. MRI has increasingly become the preferredimaging modality for evaluation of bone marrow (1,2).However, sclerotic lesions of the spine may be over-looked as they do not produce significant T2 prolon-gation. Careful evaluation of all sequences, especiallythe T1W (T1-weighted) and STIR (short tau inversionrecovery) is important. Knowledge of such lesions andtheir imaging appearances on MRI evaluation isessential for a reader. Additionally, a logical, methodi-cal approach is important to accurately diagnosethese lesions. There have been a few scattered casereports and tumor series in the literature describingthese lesions. In this article we discuss the variouscauses of spinal sclerotic lesions, describe their MRI

characteristics with relevant case examples, and out-line a systematic approach to their evaluation. The ar-ticle focuses on appearances of these lesions onconventional MRI sequences, namely, T1W, T2W,STIR, and postcontrast fat-suppressed T1W (fsT1W)imaging, as the many of these lesions might be dis-covered incidentally and the reader should know theirappearances. The role of advanced imaging, such aschemical shift imaging and diffusion imaging, is thesubject of another article.

SPECTRUM OF LESIONS

Sclerotic lesions of the spine are generally associatedwith a slow-evolving process. Although these lesions areusually evident on a plain radiographs, which is the ini-tial modality of choice, the lesions are appreciable whenone carefully looks for the marrow replacement on T1Wand T2W MR Images. These lesions typically show iso-hypointensity to the skeletal muscle on T1W images, ascompared to foci of red marrow reconversion or focalislands of fatty marrow, which show T1 hyperintensity.The lesions show variable, however predominantlyhypointense signal on T2W images and variable,although mild hyperintensity on inversion recovery(STIR) or fat-suppressed T2W (fsT2W) images due to theincreased dynamic range of contrast in the lattersequences. Although there are numerous causes ofsclerotic lesions, such as traumatic compression frac-ture, Modic type III change from chronic microtrauma,and focal anterosuperior endplate sclerosis seen withankylosing spondylitis, the spectrum of spinal scleroticlesions can be broadly classified based on the distribu-tion of the lesions as focal/multifocal and diffuse, andtheir etiologies, as depicted in Table 1.

FOCAL AND MULTIFOCAL LESIONS

Sclerotic lesions presenting as focal/multifocal lesionson MRI include bone infarct, chronic granulomatousor fungal infections, bone island, and various primaryas well as secondary neoplasms. Their pathophysiol-ogy and relevant MRI appearances are describedbelow.

1Johns Hopkins University, Baltimore, Maryland, USA2Dongguk University Gyungju Hospital, Gyungju-Si, Korea

*Address reprint requests to: A.C., Russell H. Morgan Department ofRadiology and Radiological Sciences, Johns Hopkins Hospital, 601North Caroline St., JHOC 3262, Baltimore, MD 21287. E-mail:achhabr6@jhmi.edu

Received June 6, 2012; Accepted May 7, 2013

DOI 10.1002/jmri.24247View this article online at wileyonlinelibrary.com.

JOURNAL OF MAGNETIC RESONANCE IMAGING 38:1310–1324 (2013)

VC 2013 Wiley Periodicals, Inc. 1310

Bone Infarct

Bone infarct (osteonecrosis) results from ischemiacausing necrosis of the cellular elements of the bonemarrow. It can be idiopathic or may result secondaryto a number of conditions that reduce blood supply tothe bone. Such conditions include sickle cell disease,Cushing’s disease, hemophilia, Gaucher’s disease,caissons disease (dysbaric osteonecrosis), pregnancy,systemic lupus erythematosus, steroid treatment, andradiation (3). On MRI, bone infarct is seen as patchy/geographic areas of low signal intensity with or with-out internal fat on T1W images. The lesion typicallyappears half-moon-shaped in the subchondral loca-tion. On T2W images, it typically shows a “double-line” sign which results from a hyperintense (ische-mic) inner ring and a hypointense (nonischemic) outerring (4). Acute infarcts favor fatty marrow over thehematopoietic marrow due to the limited vascularsupply of yellow marrow relative to the red marrow. Insickle cell disease, due to sickling and sequestrationof red blood cells in the red marrow, the infarcts maybe widespread (Fig. 1 and lead to typical H-shapedvertebral bodies resulting from endplate infarctions(5). To suggest this diagnosis, one should look forother associated findings, such as diffuse bone mar-row hypointensity related to hemosiderosis fromrepeated blood transfusions (Fig. 2a,b), gallstones,

autosplenectomy, and cardiomegaly may be evidentduring spine imaging.

Chronic Infection and Inflammation

Osteomyelitis refers to infection of bone and bonemarrow. It may be caused by a variety of organismsand the pathology is subdivided into acute, subacute,and chronic stages. Sclerotic/predominant hypoin-tense MRI features of osteomyelitis may be seen withchronic infections, or granulomatous disorders, suchas tuberculosis, brucellosis, and fungal infections (6).Another related inflammatory disorder is chronicrecurrent multifocal osteomyelitis (CRMO) that isassociated with SAPHO syndrome, which represents aspectrum of lesions consisting of synovitis, acne, pus-tulosis, hyperostosis, and osteitis. This conditionaffects the anterior chest wall in 65%–90% of patients,spine 33%, long bones 30%, and flat bones 10%,respectively (7).

MRI is the investigation of choice in the diagnosisand treatment evaluation of osteomyelitis following ra-diographs. The sensitivity and specificity of MRI arehigher than those of any other imaging modality avail-able (8). Typically, in vertebral osteomyelitis, there iscontiguous involvement of the vertebral body andintervertebral disk leading to decreased signal inten-sity on T1W images and corresponding increased sig-nal intensity on T2W images (5,9). These findings areassociated with longitudinal ligament edema andenhancement, vertebral destruction, and intraoss-eous, epidural, and paraspinal abscess formation. Inchronic infections, granulomatous, or fungal infec-tions, there is often mixed signal intensity, with

Table 1

The spectrum of spinal sclerotic lesions broadly classified based

upon the distribution of the lesions and their etiologies.

Focal/Multifocal sclerotic lesions Diffuse sclerotic lesions

Vascular Vascular

� Infarct � Diffuse infarction

e.g. sickle cell disease

Infection and Inflammation Primary Neoplasm

� Chronic osteomyelitis � Lymphoma/Leukemia

� CRMO/SAPHO syndrome � Multiple myeloma

(POEMS)

� Tuberculosis Secondary Neoplasm

� Fungal Infection � Metastases (Breast,

Prostate)

� Brucellosis � Lymphoma/Leukemia

Primary Neoplasm Congenital / Developmental

� Osteoid osteoma � Osteopetrosis

� Osteoblastoma � Pyknodysostosis

� Giant Cell Tumor � Fibrous Dysplasia

� Benign Notochordal Cell Tumor

� Osteosarcoma

� Multiple Myeloma (POEMS)

� Lymphoma/Leukemia

Secondary Neoplasm

� Metastases (Breast,

Prostate, Carcinoid,

Stomach, Round cell tumors)

� Lymphoma/Leukemia

Congenital/Developmental Endocrine/Metabolic

� Bone island � Pagets disease of bone

� Fibrous Dysplasia � Myelosclerosis/fibrosis

� Pagets disease of Bone � Renal osteodystrophy

� Mastocytosis

� Fluorosis

Figure 1. Sickle cell disease. Sagittal T1W image in a 19-year-old man with sickle cell disease and back pain. Noticeserpiginous fat containing lesions (arrows) in all the verte-brae in keeping with diffuse bone infarcts.

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predominant hypointensity on all imaging sequencesmimicking a sclerotic process due to a variety of fac-tors, such as insidious process (lack of proteolytic en-zymatic degradation seen with bacterial infections),reactive body response, calcifications, and bony pro-ductive changes (Fig. 3a,b) (10). Underlying immuno-suppression, chronic symptomatology of back painand weight loss, elevated sedimentation rate, positiveskin test for tuberculosis, and clinical findings ofSAPHO syndrome serve as useful hints towards theimaging diagnosis (9).

Benign Neoplasm

Primary neoplasms of the spine presenting as scle-rotic (T2 dark) lesions are categorized as benign path-ologies (enostosis, osteoid osteoma, osteoblastoma,and giant cell tumor) or malignant pathologies (osteo-sarcoma, myeloma, lymphoma, leukemia, and metas-tases) (11).

Enostosis

Enostosis or bone island is a focus of compact bonelocated in cancellous bone. Bone islands are usuallyfound incidentally on the imaging studies. A boneisland larger than 1 cm is referred to as a giant boneisland (12). Bone islands demonstrate uniformly lowsignal intensity on T1W and T2W MRI scans. They arefrequently oval-shaped, show trabeculated margins,and are oriented along the long axis of the bone,much unlike sclerotic metastasis, which are usuallyround and show smooth margins (Fig. 4. Additionally,other aggressive features, such as bone marrowedema, soft tissue mass, cortical destruction, andperiostitis are absent with bone islands (12).

Osteoid Osteoma

Osteoid osteoma is a benign neoplasm that arisesfrom osteoblasts. It most commonly occurs betweenthe ages of 7 and 25 (male:female ratio 2:1) and iscomposed of osteoid and woven bone. The tumor isusually smaller than 1.5 cm in diameter (13,14). Inapproximately two-thirds of patients, the appendicu-lar skeleton is involved. Ten to twenty percent oftumors occur in the spine, with the commonest loca-tion being the lumbar vertebrae (59%), and in major-ity of the cases the nidus is located in the neural arch(15). The clinical presentation is often a dull bonepain that worsens at night as well as with activity,and is dramatically relieved with small doses of non-steroidal antiinflammatory drugs (NSAIDS). When itaffects the spine, the lesion is associated with severelower back pain and scoliosis (15). On MRI, the nidusis isointense to the muscle on T1W and hyperintenseon T2W sequences, respectively. There is accompany-ing peri-nidus edema, periostitis, and surroundingsclerosis, which contribute to mixed signals on T2Wimages (Fig. 5 (15). Dynamic gadolinium-enhancedMRI has been shown to demonstrate the nidus andperi-nidus edema with increased conspicuity com-pared with nonenhanced MRI (14,16).

Osteoblastoma

Osteoblastoma shares very similar tissue morphology,clinical pathology, and histology with osteoid osteoma(17). Osteoblastoma, however, is a larger (2–6 cm)lesion (Fig. 6 and in almost a quarter of cases followsa more aggressive course with local growth and dis-tant metastases (14). The MRI features are similar towhat a larger osteoid osteoma would look like, withsometimes associated soft tissue mass or aggressivebehavior, and distant metastases.

Giant Cell Tumor

Giant cell tumors occur in young and middle-agedpatients (women:men ratio 2:1), and consist of multi-ple multinucleated giant cells (18). When they occurin the spine, they are 3–4 times more common in thesacrum as compared to the rest of the spine (19). Thepart of the vertebra that is most commonly affected is

Figure 2. Sickle cell disease marrow. Coronal T1W (a) andfsT2W (b) images in a skeletally immature patient with sicklecell disease. Notice diffuse marrow hypointensity on bothimages due to red marrow reconversion and hemosiderosis.

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the body rather than the neural arch (20). On T1Wimages, giant cell tumors may show heterogeneous orhomogeneous, predominantly isointense signal inten-sity characteristics with areas of high signal intensity,caused by recent hemorrhage. While these lesionsappear lytic on plain films, on T2W images, heteroge-neous low signal intensity is seen in the solid areas of

the tumor (Fig. 7 (21). Areas of low signal intensitymay be exaggerated on the gradient-echo images dueto the presence of hemosiderin. Hemosiderin is pres-ent in more than 63% of giant cell tumors, and itspresence is probably the result of extravasated redblood cells coupled with the phagocytic function ofthe tumor cells. Fluid–fluid levels may be seen due tosuperimposed aneurysmal bone cyst (20). The tumorshows heterogeneous enhancement on intravenouscontrast administration (20).

Figure 3. a: TB osteomyelitis. Sagittal T2W image in a 54-year-old woman with back pain and fever. There is heterogeneouslyhypointense to isointense marrow signal changes with intervertebral disc extension (arrows). b: TB osteomyelitis. Note intenseenhancement with central necrosis on fsT1W image in this biopsy-proven case of tuberculosis.

Figure 4. Enostosis. Sagittal T2W image in a 67-year-oldwoman with incidental finding of sclerotic lesion on imaging.There is markedly hypointense lesion in L3 vertebra with tra-beculated margins and no associated bone marrow edema inkeeping with a bone island (arrows).

Figure 5. Osteoid osteoma. Axial T2W image of the lumbarvertebra in a young patient with painful scoliosis. Notice aheterogeneously hypointense mass in the right-sided neuralarch (small arrows) and associated extensive bone marrow(large arrows) and fascial edema.

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MALIGNANT NEOPLASM

Osteosarcoma

Osteosarcoma is the second most common primarymalignant tumor of bone, following plasma cell (multi-ple) myeloma. It arises from the primitive transformedmesenchymal cells. Overall, 75% of osteosarcomalesions are the classic (conventional) type (22). Theincidence is estimated at 5.0 per million per year inthe general population, being slightly higher in theblack and Hispanic populations (6.8 and 6.5 permillion per year, respectively) than in the white popu-lation (4.6 per million per year) (23). Spinal osteosar-coma accounts for 3.6%–14.5% of primary spinaltumors and 1.7%–2.9% of all osteosarcomas (24). Menare slightly more commonly affected (5.4 per millionper year) than women (4.0 per million per year). Flatbone involvement including vertebral lesions is lesscommonly seen than with chondrosarcoma and isusually observed in the older population as comparedto appendicular osteosarcoma (25).

MRI offers the most important information for theaccurate local staging of osteosarcoma; it provides in-formation on the compartmentalization of the diseaseand therefore assists in determining the most appro-priate management (26). The lesion shows large areasof new bone formation and predominant hypointenseareas on all sequences (Fig. 8a,b). T1W spin-echosequence provides the most accurate assessment ofthe extent of the bone tumor in the longitudinal direc-tion. STIR sequences are slightly more sensitive, whileT1W sequences are slightly more specific. STIR andfat-suppressed T2W sequences are the most accuratein evaluation of the neurovascular bundle. Dynamiccontrast enhanced MRI has been shown to be effectivein characterizing, staging, biopsy targeting, and evalu-ation of treatment response for osteosarcoma (27,28).

Diffuse Sclerotic Lesions

Sclerotic lesions presenting as diffuse lesions on MRIinclude: osteopetrosis, pyknodysostosis, fibrous dys-plasia, Paget’s disease, renal osteodystrophy, masto-cytosis, fluorosis, and various primary as well assecondary neoplasms, such as sclerotic multiple my-eloma (POEMS), lymphoma, leukemia, and osteoblas-tic metastatic lesions (Table 1. Their pathophysiologyand relevant MRI appearances are described below.

Multiple Myeloma/POEMS

Multiple myeloma is the most common primary malig-nant neoplasm of the skeletal system. It is a monoclo-nal proliferation of plasma B cells with infiltration ofbone marrow. The disease develops in 1–4 per100,000 people per year. It is more common in men,and is twice as common in African Americans as com-pared to whites (29–31).

MRI provides a superior soft-tissue contrast resolu-tion for the diagnosis of multiple myeloma. The my-eloma deposit is characteristically a round, low signalintensity focus on T1W images, which becomes highin signal intensity on T2W sequences. MRI has beenshown, in some studies, to provide important prog-nostic information. The presence of more than sevenfocal lesions or diffuse disease has been shown to bean independent predictor of poorer prognosis. Con-versely, the complete resolution of focal lesions hasbeen shown to be strong predictor of survival (32).

Sclerotic lesions in myeloma are seen in about 3%of cases (33). These lesions show relatively slowergrowth and have a better prognosis than the classicform. On MRI, the lesions show predominantly low

Figure 6. Osteoblastoma. Axial T1W image of the cervicalvertebra in a young patient with neck pain. Notice a hetero-geneously hypointense mass in the right-sided neural arch(small arrows), >1.5 cm and penetrating the posterior cortexof the right lamina (large arrow).

Figure 7. Giant cell tumor (GCT). Sagittal T2W image in a31-year-old woman with back pain and bilateral leg painwith weakness. There is a heterogeneous, predominantlyhypointense lesion involving S1–3 vertebrae with extensioninto the spinal canal, a biopsy-proven GCT.

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signal intensity on all imaging sequences. Polyneurop-athy, organomegaly, endocrinopathy, monoclonalgammopathy, and skin changes (POEMS) syndrome isa multisystemic disease that rarely complicates scle-rotic multiple myeloma or other plasma cell dyscra-sias (Fig. 9a,b) (34). The pathophysiology underlyingthe disease is not well understood; however, it isthought to be related to excessive and inappropriate

cytokine and growth factor production (35). Othercauses of sclerosis in myeloma lesions include super-imposed infection or development of amyloidosis.

Leukemia/Lymphoma

Based on WHO criteria, there are four types of lym-phoma that involve bone: Group 1, lymphoma with a

Figure 8. Osteosarcoma. Sagittal T1W (a) and T2W (b) MR images of the LS spine in a 57-year-old man with low back painand leg weakness. Notice the heterogeneously hypointense lesion involving the S1 and S2 vertebrae (arrow) with associatedcortical destruction and intraspinal soft-tissue mass, a biopsy-proven osteosarcoma.

Figure 9. POEMS. Sagittal T1W (a) and T2W (b) images in a patient 38-year-old woman with known POEMS syndrome. TheLS spine images show heterogeneously T1 and T2 hypointense lesion in the right lateral mass of L2 vertebra (arrow). Anotherlesion with similar characteristics was seen in the sacrum (not shown).

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single bone site with or without regional lymph-nodeinvolvement; Group 2, lymphoma with multiple bonesinvolved, but no visceral or lymph-node involvement;Group 3, bone tumor with involvement of other vis-ceral sites or lymph nodes at multiple sites; andGroup 4, lymphoma involving any other sites andfound by bone biopsy (36). Groups 1 and 2 are con-sidered primary bone lymphoma (PBL) and are rare,whereas Groups 3 and 4 are considered distant me-tastasis and are, by definition, Stage 4 diseases. PBLaccounts for 3% of primary bone tumors and 5% ofextranodal lymphomas. Secondary bone involvementoccurs in 5%–15% of Hodgkin’s and 30%–50% of non-Hodgkin’s lymphomas (37). The peak prevalenceoccurs in the 5th–7th decades, with a strong malepredominance (male:female ratio 8:1) (38).

Non-Hodgkin’s lymphoma accounts for most spinalcases and is associated with a lytic, sclerotic (ivoryvertebrae), or mixed reaction (39). MRI shows a focal/multifocal pattern or diffuse infiltration, with iso-hypointensity on T1W images and a predominantlyhomogeneous increase in intensity on T2W images.Epidural involvement and spinal cord compression isalso clearly delineated on MRI. Tumor extension intothe soft tissues is a common feature of lymphoma asopposed to metastases, and is often associated withcortical permeation, which refers to the spread of tu-mor through the fine vascular channels withoutdestruction of the cortical integrity (40).

Leukemia is associated with diffuse bone involve-ment, rather than focal lesions as seen with lym-phoma. The normal bone marrow is completelyreplaced by the abnormal tissue. The intervertebraldiscs appear brighter or isointense to the diseasedmarrow. T1W images display a diffuse reduction inthe signal intensity of the marrow, whereas T2Wimages display a variable increase in the signal inten-sity. This increase in signal may be difficult to appre-ciate because there is no normal marrow forcomparison (41). Dynamic contrast-enhanced (DCE)-MRI shows significant enhancement of the abnormalmarrow and intervertebral discs appear darker thanthe enhanced marrow (Figs. 10a,b, 11 (42).

Osteoblastic Metastatic Lesions

Metastatic sclerotic bone lesions present in three typi-cal patterns, focal, variegated, or diffuse based on thehistological origin of the primary tumor. The mostcommon focal metastatic lesions originate from thebreast (37%), lung (15%), kidney (6%), and thyroid(4%) (43). Sclerotic metastases arise from prostate,breast, neuro-endocrine tumors, and stomach. Typi-cally, they appear in a solitary nodular pattern con-sisting of localized areas of abnormal marrow. OnT1W images, the focal lesions are darker than yellowmarrow and slightly darker or isointense to red mar-row. On fsT2W and STIR images, these are minimally

Figure 10. a: Lymphoma. Sagittal T2W image in a middle-aged patient with known B-cell systemic lymphoma, presentingwith back pain. Images show extensive vertebral involvement with diffuse low T2 signal changes. Also note the associatedcortical permeation and homogeneous soft-tissue mass in prevertebral tissues and spinal canal (arrows). b: Lymphoma. F18-FDGPET scan in the same patient showing significant glucose uptake in multiple spine and pelvic lesions (arrows).

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brighter than both red and yellow marrow and may besurrounded by a rim of hyperintense signal. This so-called “halo sign” has a sensitivity of 75% and speci-ficity of 99.5% (44). On CE-MRI, T1W images showmarked enhancement compared to the surroundingmarrow due to the vascularity of the underlying path-ologic process. STIR and fat-saturation T2W imagesprovide increased contrast between focal lesions anduninvolved marrow (Fig. 12a–c) (44).

Fibrous Dysplasia

Fibrous dysplasia results from a defect in osteoblasticdifferentiation and maturation that replaces the med-ullary bone matrix with fibrous tissue. It can be mon-ostotic (single bone affected) or polyostotic (multiplebone involvement) (45). A combination of caf�e au laitspots, endocrine disorders, precocious puberty, andpolyostotic fibrous dysplasia is described as McCune-Albright syndrome. It is caused by a missense muta-tion in chromosome 20q13. This mutation resultsin osteoblastic differentiation defects and an increasein bone resorption (46).

On MRI, the lesions show iso-hypointense signal in-tensity on T1W images and predominantly low signalintensity on T2W images. Additional features of well-defined lesional margins, cortical thickening fromremodeling, and clear halo of perilesional fat on T1Wimages in young patients are useful diagnostic fea-tures. Ground glass matrix related to high content ofcollagen, commonly seen on radiographs, does not

produce a characteristic signature on MRI; however,the lesions are sharply defined without significantbone marrow edema (Fig. 13a,b) (47).

Paget’s Disease

Osteitis deformans (Paget’s disease [PD]) refers to achronic condition in which excessive breakdown(osteoclastic activity) and formation (osteoblastic ac-tivity) of bone tissue causes affected bone to weaken.It typically shows fibrofatty marrow changes, trabecu-lar disorganization, cortical involvement, and verte-bral expansion leading to chronic bone pain, nerveand spinal cord impingements, and compressiondeformities. The prevalence of PD in the U.S. is �1%of the population. The spine is the second most fre-quently affected region after the pelvis (48). PD nor-mally affects people over 40 years of age (men:womenratio 1.8:1) (49) and occurs more frequently in Cauca-sians (50). PD is linked to both genetic predisposition(sequestrosome 1 gene and PDB3 region on chromo-some 5) (51,52) and viral infection from the paramyx-ovirus family (canine distemper virus) (53). PD evolvesthrough three stages: 1) an early lytic or hot phase; 2)an intermediate or mixed phase; and 3) a final blasticor cold phase, marked by dense bone formation (54).

On MRI, bone marrow signal intensity evolvesthrough three stages. In Stage 1, there is low T1W in-tensity and high T2W intensity due to replacement offatty marrow with hypervascular marrow (55). Duringthe mixed phase, there is low T1 with mildly higherT2 intensity. The mixed phase is associated with thecharacteristic picture-frame vertebrae (56). The blasticor sclerotic phase has two consecutive stages. Thefirst is the fibrotic stage which occurs early, resultingin low T1- and T2-intensity because of increased mar-row fibrosis. The later stage is the fatty transforma-tion, resulting in hyperintensity on both T1W andT2W images. The sclerotic phase is associated withthe ivory vertebrae (56). There is a significant correla-tion of bone circulation and bone turnover in PD.DCE-MRI has been shown to be an effective diagnos-tic tool for monitoring therapeutic effects of bisphosh-onates in PD of bone (Fig. 14a–c) (54).

Myeloproliferative/Myelodysplastic Disorders

Polycythemia vera, essential thrombocythemia, andprimary myelofibrosis belong to the group of chronicmyeloproliferative disorders. In patients with Polycy-themia rubra vera, and essential thrombocythemia,the bone marrow of the axial skeleton is hypercellularand, therefore, is diffusely and homogeneously hypo-intense on T1W and high signal intensity on T2W MRimages. Foci of hypercellular marrow may appear inthe peripheral skeleton as well. In primary myelofibro-sis, however, the bone marrow may be hypercellularor depleted of all hematopoietic elements. Fibroticmarrow is characteristically visualized as areas ofmarkedly low signal on T1W, T2W, and STIR sequen-ces (57). Unless the characteristic appearance offibrotic marrow is seen, myelofibrosis cannot be

Figure 11. Treated leukemia. Sagittal T2W MR image in apatient completing chemotherapy for leukemia. Image showsvariegated, multifocal, low intensity foci in the background ofnormal fatty marrow in keeping with treated leukemia.

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distinguished from other hematologic malignancieswith MR images alone (Fig. 15 (57).

The myelodysplastic syndromes (MDS) are a diversecollection of hematological conditions that involveineffective production of the myeloid class of bloodcells. The loss of the long arm of chromosome 5 hasbeen associated with some of the dysplastic abnor-malities of hematopoietic stem cells (58). MDS includerefractory anemia, refractory anemia with ringed side-roblast, refractory anemia with excessive blasts, andrefractory anemia with excessive blast in transforma-tion. MR images of refractory anemia are diagnosticbecause of the absence of cellular elements and thepresence of abundant fatty marrow. The signal inten-sity of the aplastic bone marrow on T1W and T2Wimages approaches that of subcutaneous fat. The

characteristic fatty appearance of the aplastic marrowmay not be observed in the presence of hemosidero-sis, because the deposition of iron causes a decreasein the signal of the bone marrow on T1W and, particu-larly, on T2W images (59). Studies have shown that inpatients with myelodysplastic syndromes an increasein the extent of marrow abnormality and in its signalintensity on STIR images indicate a higher chance ofprogression to acute myeloid leukemia (60).

Renal Osteodystrophy

This refers to a spectrum of bony changes resultingfrom deranged renal function, such as osteomalacia,secondary hyperparathyroidism, and osteosclerosis(61,62). The pathophysiology of osteosclerosis is

Figure 12. Breast metastasis. Sagittal T1W (a) and STIR (b) images in a patient with known breast cancer, presenting withback pain. Images show diffuse metastatic infiltration of the spinal vertebrae (arrows) with moderate collapse of L5 vertebra.c: Breast metastasis. Axial T2W image in the same patient shows multifocal metastatic infiltration of the liver (arrows).

1318 Mugera et al.

poorly understood but is thought to be a result ofabnormal activation of osteoclasts and osteoblastswith increased cancellous bone deposition containingamorphous calcium phosphate rather than the hy-droxyapatite (63).

MRI shows diffuse bone marrow changes associatedwith renal osteodystrophy, such as red marrow recon-version, hemosiderosis, bone deformity, cortical thick-ening, and irregular trabecular patterns. Low T1Wand T2W signal along the endplates may give thecharacteristic rugger-jersey appearance (64). Whilemarrow reconversion results in low T1W signal inten-sity that increases variably on T2W and STIR sequen-ces (65), hemosiderosis results in hypointensemarrow signal in all sequences as a result of themagnetic susceptibility (Fig. 16a,b). Additionally, onemight see accompanying diffuse hypointensity of theabdominal viscera, such as spleen and liver (65). Inci-dental inclusion of kidneys may also reveal corticalatrophy, renal sinus lipomatosis, or polycystic kidneydisease.

Mastocytosis

Mastocytosis represents a spectrum of diseases char-acterized by mast cell proliferation in different tissuesof the body. The disorder ranges from the cutaneousform of urticaria pigmentosa to systemic mastocytosisand mast cell leukemia. Urticaria pigmentosa occursmostly in the pediatric age group and accounts for

80%–90% of cases. Systemic mastocytosis (SM)accounts for less that 10% of mastocytosis but affectsadults almost exclusively. Skeletal involvement with aspecial tropism for the axial skeleton occurs in 70% ofcases of SM (66). The lesions can be both lytic andsclerotic, as well as both focal or diffuse. The lyticlesions are a result of the release of chemical media-tors by mast cell aggregates. The sclerotic lesions, inturn, are produced by the fibrotic and osteoid deposi-tion stimulated by histamine release. The clinical pre-sentation is commonly asymptomatic, although it maycause pain, tenderness, or pathological fractures as aresult of trabecular destruction (67). The typical MRIfeatures of bone marrow show diffuse or multifocalfeatures of nonfatty cell infiltration, with a replace-ment of the normal high signal and a homogenoushypointense signal on T1W MR images and mixed sig-nal intensity on T2W and STIR sequences (Fig. 17a,b)(68). Multifocal bubbly lesions may be identified andmultifocal or diffuse enhancement may be seen onpostcontrast fsT1W images. In one series Haney et al(66) described fluid levels in addition to the presenceof multifocal lesions in the lumbar vertebrae.

Pyknodysostosis and Osteopetrosis

Pyknodysostosis is an autosomal recessive lysosomalstorage disorder caused by a mutation in the genethat codes the protease enzyme cathepsin K on thelong arm of chromosome 1 (69). Deficiency of this

Figure 13. Fibrous dysplasia. Sagittal T1W (a) and axial T2W (b) images in a patient with known polyostotic fibrous dyspla-sia. Images show multifocal hypointense lesions on both sequences with well-defined margins (arrows). No associated bonemarrow edema or soft-tissue mass is seen.

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protease produces dysfunctional osteoclasts resultingin osteosclerosis. Features include: short stature (lessthan 150 cm / 59 inches), scoliosis, short distal pha-langes (acroosteolysis), open fontanels, obtuse man-dibular angle, dysplastic clavicle, brittle bones, aswell as retained deciduous teeth (70).

Osteopetrosis is a syndrome associated with amutation in the gene that codes the enzyme carbonicanhydrase II on the long arm of chromosome 8. Defi-ciency of this enzyme produces dysfunctional osteo-clasts resulting in osteopetrosis (71). There are threeclassical presentations: The autosomal dominant formis a mild adult-onset disease found incidentally onimaging. The childhood form is an autosomal

recessive disease and is associated with a poor prog-nosis (72). The infantile form is even more aggressiveand has an even worse prognosis. The causes of deathare bone marrow failure, anemia, and infections. Theautosomal dominant form has two phenotypes: inType I, the findings are sclerotic thickening of the cal-varium, most prominent in the vault, with mild sclero-sis, and increased density of the vertebral arches. InType II, the base of the skull is sclerotic but the calva-rium is nearly normal and there is thickening of thevertebral endplates. Patients with Type II are at highrisk of fracture, while Type I patients are not (72).

T1W MR images of the spine in both disorders showabsence of high signal usually seen in the normal fatty

Figure 14. Paget’s disease. Sagittal T1W (a) and T2W (b) images in a patient being follow-up for failed back surgery. Imagesshow a hypointense lesion replacing the L2 vertebra with a picture frame appearance (arrows). c: Pagets disease. Correspond-ing axial T1W image in the same patient shows mixed fibro-fatty change with peripheral hypointense rim (arrows).

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marrow of the skull and vertebrae. T2W MR imagesalso shows diffuse low signal (Fig. 18. In addition, sag-ittal T1W images show vertebral thickening and hypo-intensity as well as thickened calvarium and base ofskull. T2W images confirm spinal canal stenosis andnerve impingement and atrophy (73). The occurrenceof lumbar and cervical spondylolysis in the setting ofosteopetrosis has been reported by multiple authors(74,75). Spondylolysis on MRI appears as increasedsignal on T2W and decreased signal on T1W images inthe pars interarticularis reflecting marrow edema (76).

KEY POINTS

1. Recognize the marrow replacement on T1Wimages, which are more sensitive and specificthan T2W images.

2. Correlate with available plain radiographs.3. Classify the lesions in focal/multifocal and diffuse.4. Look for typical features: For focal lesions, bone

island (trabeculated margin), infections (soft tis-sue edema, collection, and disc involvement),osteoid osteoma (classic location, size <1.5 cm,and nidus), osteoblastoma (classic location, simi-lar to osteoid osteoma, but >1.5 cm), giant celltumor (20–40 age group, more common infemales, vertebral body predilection, secondaryABC with fluid-fluid levels), osteosarcoma (sunray spicules, heterogeneous soft-tissue mass),metastases (known primary malignancy, mostcommon lesion at age >40 years, peripheral high

Figure 16. a: Renal osteodystrophy. Sagittal T2W image in a patient on hemodialysis patient shows diffuse low signal inten-sity due to a combination of red marrow reconversion and hemosiderosis. b: Renal osteodystrophy. Axial image in the samepatient shows atrophic kidneys with renal sinus lipomatosis.

Figure 15. Myelofibrosis. Sagittal T2W image in a 65-year-old man with pancytopenia and known myelofibrosis pre-senting with back pain. The image shows heterogeneous dif-fuse low marrow signal, isointense to the skeletal muscle.Vertebral bodies as well as posterior elements are involved.Also note bone marrow edema (arrows) across the L4–5 disc,which turned out to be superimposed osteomyelitis.

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signal rim on T2W images), and sclerotic my-eloma (POEMS syndrome).

5. Look for typical features: For diffuse lesions,sickle cell disease (diffuse red marrow reconver-sion, hemosiderosis, endplate infarcts, autosple-nectomy, gall stones, cardiomegaly), fibrousdysplasia (young age, well-defined scleroticlesions with halo of fat and cortical thickening),

Paget’s disease (older age, vertebral expansion,cortical thickening, fibrofatty marrow), osteopet-rosis (young age, diffusely low marrow signal in-tensity, banana fractures), pyknodysostosis(young age, mandibular angle widening, acro-os-teolysis), renal osteodystrophy (renal abnormal-ities, red marrow reconversion, andhemosiderosis), mastocytosis (urticaria, multifo-cal well-defined lesions: bubbly or with fluidlevels).

6. Look for typical features: For lesions, which canbe either focal/diffuse, lymphoma/leukemia(multifocal or diffuse lesions, homogeneity, corti-cal permeation, homogeneous soft tissue mass),POEMS, metastases, fibrous dysplasia, andPaget’s disease, as described above.

To conclude, sclerotic lesions of the spine arecaused by a variety of pathologies and these lesionsoften do not produce significant T2 prolongation onMR images. Knowledge of such pathologies and a pru-dent use of a systematic MR interpretation approachare essential for appropriate and timely diagnosis.

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