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1 MR Evaluation of Bone Marrow Disorders Nisha Patel, MD.

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1 1 MR Evaluation of Bone Marrow Disorders Nisha Patel, MD

2 2 Introduction Nearly all imaging modalities evaluate the marrow, which is a site of significant pathology Nearly all imaging modalities evaluate the marrow, which is a site of significant pathology  Radiography  Nuclear Medicine  CT  MR

3 3 Topics of Discussion Normal marrow anatomy and function Normal marrow anatomy and function MRI appearance of normal marrow MRI appearance of normal marrow Benign and malignant marrow pathology Benign and malignant marrow pathology

4 4 Normal Marrow Anatomy and Function Three basic marrow components: Three basic marrow components:  Trabeculae  Red marrow  Yellow marrow

5 5 Trabeculae Serve as the architectural support for the marrow and as a mineral depot. Serve as the architectural support for the marrow and as a mineral depot. Number of trabeculae decreases with age. Number of trabeculae decreases with age.

6 6 Red Marrow Composed of hematopoietic cellular elements (red and white cells and platelets), supporting stroma (reticulum), and rich sinusoidal vascular supply Composed of hematopoietic cellular elements (red and white cells and platelets), supporting stroma (reticulum), and rich sinusoidal vascular supply Smaller fraction of fat cells (40%) Smaller fraction of fat cells (40%) It increases if the demand for hematopoiesis increases It increases if the demand for hematopoiesis increases

7 7 Yellow Marrow Smaller fraction of red marrow elements. Smaller fraction of red marrow elements. Larger fraction of fat cells (>50%) Larger fraction of fat cells (>50%) Poor vascular supply Poor vascular supply Paucity of reticulum Paucity of reticulum Increases with age Increases with age

8 8 Topics of Discussion Normal marrow anatomy and function Normal marrow anatomy and function MRI appearance of normal marrow MRI appearance of normal marrow Benign and malignant marrow pathology Benign and malignant marrow pathology

9 9 MRI Appearance of Normal Marrow T1W SE and STIR are most commonly used sequences to evaluate the marrow. T1W SE and STIR are most commonly used sequences to evaluate the marrow. In general, yellow marrow follows the signal intensity of subcutaneous fat, with relatively high signal on T1W images and low signal on STIR images. In general, yellow marrow follows the signal intensity of subcutaneous fat, with relatively high signal on T1W images and low signal on STIR images. Red marrow follows the signal intensity of muscle and has an intermediate signal intensity on T1W images and STIR images. Red marrow follows the signal intensity of muscle and has an intermediate signal intensity on T1W images and STIR images.

10 10 Marrow Conversion Amount and distribution of red and yellow marrow changes with time as well as in response to physiologic stresses Amount and distribution of red and yellow marrow changes with time as well as in response to physiologic stresses Normal conversion of red to yellow marrow occurs in a predictable and progressive manner Normal conversion of red to yellow marrow occurs in a predictable and progressive manner At birth, nearly the entire osseous skeleton is composed of red marrow. At birth, nearly the entire osseous skeleton is composed of red marrow. Conversion proceeds from the appendicular (distal to proximal extremities) and then to the axial skeleton in a bilateral symmetric fashion. Conversion proceeds from the appendicular (distal to proximal extremities) and then to the axial skeleton in a bilateral symmetric fashion.

11 11 Within an individual long bone, conversion occurs in the following sequence: Epiphysis and apophysis  Diaphysis  Distal metaphysis and proximal metaphysis

12 12 Marrow Conversion in Long Bones Infantile (0-1y) Infantile (0-1y) Childhood (1-10y) Childhood (1-10y) Adolescent (10-20y) Adolescent (10-20y) Adult (25+) Adult (25+)

13 13 Infantile pattern 0-1 year 0-1 year Homogeneous low signal marrow in diaphyses and metaphyses Homogeneous low signal marrow in diaphyses and metaphyses

14 14 Childhood pattern 1-10 year 1-10 year Higher signal in diaphyses and metaphyses representing red  yellow marrow conversion Higher signal in diaphyses and metaphyses representing red  yellow marrow conversion

15 15 Adolescent pattern year year Distal metaphyseal marrow converts to yellow marrow Distal metaphyseal marrow converts to yellow marrow Residual islands of red marrow leave a heterogeneous pattern to the metaphyseal marrow Residual islands of red marrow leave a heterogeneous pattern to the metaphyseal marrow

16 16 Adult pattern 25 years + 25 years + Predominant homogeneous high signal diaphyseal and metaphyseal marrow Predominant homogeneous high signal diaphyseal and metaphyseal marrow Hematopoietic marrow concentrated in the axial skeleton (skull, ribs, vertebra, sternum, pelvis) and to a lesser degree in the proximal appendicular skeleton (proximal femora and humeri) Hematopoietic marrow concentrated in the axial skeleton (skull, ribs, vertebra, sternum, pelvis) and to a lesser degree in the proximal appendicular skeleton (proximal femora and humeri)

17 17 Adult pattern After adult pattern reached, there is continued and gradual further replacement of hematopoietic marrow with fatty marrow After adult pattern reached, there is continued and gradual further replacement of hematopoietic marrow with fatty marrow Spine and pelvis on T1 in elderly reflect this change Spine and pelvis on T1 in elderly reflect this change

18 18 Topics of Discussion Normal marrow anatomy and function Normal marrow anatomy and function MRI appearance of normal marrow MRI appearance of normal marrow Benign and malignant marrow pathology Benign and malignant marrow pathology

19 19 Bone Marrow Abnormalities Two USEFUL variables Two USEFUL variables  Distribution of normal hematopoietic marrow  Has a characteristic distribution based on age and functional status  Thorough knowledge is important as any variation can represent disease  Signal intensity  Muscle or Disc serve as internal control  Normal marrow signal: isointense/hyperintense to muscle or disc on T1W  Diseased marrow: hypointense T1 signal compared to the muscle or disc

20 20 Marrow Pathology Disorders of marrow proliferation Disorders of marrow proliferation Disorders of marrow replacement Disorders of marrow replacement Disorders of marrow depletion Disorders of marrow depletion Vascular and Miscellaneous abnormalities Vascular and Miscellaneous abnormalities

21 21 Marrow Proliferative Disorders Arise from the proliferation of cells that normally exist in the marrow Arise from the proliferation of cells that normally exist in the marrow Involve the marrow in a diffuse manner (except for focal multiple myeloma) Involve the marrow in a diffuse manner (except for focal multiple myeloma)

22 22 Marrow proliferative disorders Benign Benign   Marrow reconversion   Mastocytosis   Amyloidosis Malignant   Polycythemia Vera   Myeloid Metaplasia with Myelofibrosis   Waldenstrom’s macroglobulinemia   MM   Leukemia

23 23 Marrow Reconversion Reconversion is due to increased demand for hematopoiesis. Reconversion is due to increased demand for hematopoiesis. Can be seen in hemolytic anemias, high level athletes, GCSF therapy, smokers, and destruction of red marrow. Can be seen in hemolytic anemias, high level athletes, GCSF therapy, smokers, and destruction of red marrow.

24 24 Marrow Reconversion

25 25 Mastocytosis Rare disorder characterized by mast cell proliferation Most commonly occurs as a skin manifestation (urticaria pigmentosa- generally a self-limited dermatologic disorder in children) Systemic form rarer and involves the bone marrow and internal organs Xrays   Lytic or sclerotic lesions in a focal or diffuse distribution MR   Nonspecific pattern ranging from normal, focally/diffusely heterogeneous   Typically involves axial skeleton

26 26 Courtesy of Tudor Hughes, M.D.

27 27 Courtesy of Tudor Hughes, M.D.

28 28 Myeloproliferative disorders Group of diseases Group of diseases  Polycythemia rubra vera  Agnogenic myeloid metaplasia (AMM) (Idiopathic myelofibrosis)  CML  Essential thrombocytopenia Older patients (6th-8th decade) Older patients (6th-8th decade) Malignant transformation of pluripotent stem cells resulting in expansion of various BM elements Malignant transformation of pluripotent stem cells resulting in expansion of various BM elements PV and AMM have similar MR appearance PV and AMM have similar MR appearance  Diffuse intermediate T1 signal Myelofibrosis Myelofibrosis  Diffuse/Patchy sclerotic bone  Low T1 and T2 signal

29 29 Courtesy of Tudor Hughes, M.D. Polycythemia Vera

30 30 Courtesy of Tudor Hughes, M.D. Myelofibrosis

31 31 Courtesy of Tudor Hughes, M.D. Myelofibrosis

32 32 Leukemia Acute: diffuse skeletal involvement Acute: diffuse skeletal involvement Chronic: (adults) involve areas of residual marrow in pelvis, spine, femurs Chronic: (adults) involve areas of residual marrow in pelvis, spine, femurs Involvement of the epiphyses/apophyses at any age reflects higher tumor burden Involvement of the epiphyses/apophyses at any age reflects higher tumor burden

33 33

34 34 Multiple Myeloma (MM) Most common primary bone tumor Most common primary bone tumor Solitary (plasmacytoma) form and more common multiple (myeloma) form Solitary (plasmacytoma) form and more common multiple (myeloma) form Xrays Xrays  Solitary lytic lesion or numerous focal punched out lesions  Generalized osteopenia MRI patterns of MM in order of increasing frequency: MRI patterns of MM in order of increasing frequency:  normal (low tumor burden)  focal lesion  heterogeneous (variegated)  homogenous (diffuse)

35 35

36 36 Angtuaco, E. J. C. et al. Radiology 2004;231:11-23

37 37 Marrow Pathology Disorders of marrow proliferation Disorders of marrow proliferation Disorders of marrow replacement Disorders of marrow replacement Disorders of marrow depletion Disorders of marrow depletion Vascular and Miscellaneous abnormalities Vascular and Miscellaneous abnormalities

38 38 Marrow Replacement Disorders Implantation of cells in the marrow that do not normally exist there Implantation of cells in the marrow that do not normally exist there Usually focal lesions Usually focal lesions MRI appearances include low T1 signal (equal or less than muscle or disc) and variable T2 signal (usually high, unless sclerotic). MRI appearances include low T1 signal (equal or less than muscle or disc) and variable T2 signal (usually high, unless sclerotic).

39 39 Marrow Replacement Disorders Benign Benign   Primary Bone tumors   Osteomyelitis Malignant   Metastasis   Lymphoma   Malignant Bone tumors

40 40 Metastasis Common primaries: breast, lung and prostate Common primaries: breast, lung and prostate Involve red marrow in spine, pelvis, prox femurs and humeri Involve red marrow in spine, pelvis, prox femurs and humeri Focal lesions with low T1 and high T2 and variable surr. edema Focal lesions with low T1 and high T2 and variable surr. edema

41 41 Lymphoma Primary lymphoma of bone rare NHL > HD Xray   Permeative and lytic   Appendicular skeleton in diaphyses of femur, tibia and humerus

42 42 Krishnan, A. et al. Radiographics 2003;23:

43 43

44 44 Marrow Pathology Disorders of marrow proliferation Disorders of marrow proliferation Disorders of marrow replacement Disorders of marrow replacement Disorders of marrow depletion Disorders of marrow depletion Vascular and Miscellaneous abnormalities Vascular and Miscellaneous abnormalities

45 45 Marrow Depletion Disorders Due to ablation of red marrow elements Due to ablation of red marrow elements Involvement can be diffuse or regional in distribution Involvement can be diffuse or regional in distribution 3 main causes include chemotherapy, radiation, and aplastic anemia 3 main causes include chemotherapy, radiation, and aplastic anemia MRI appearances follow the signal intensity of fat MRI appearances follow the signal intensity of fat

46 46 Chemotherapy Systemically destroys normal hematopoietic marrow and tumor cells Systemically destroys normal hematopoietic marrow and tumor cells 1st week post chemo 1st week post chemo  Edematous and hypocellular marrow Post 1st week Post 1st week  Progressive fat replacement of marrow (similar to untreated aplastic anemia)

47 47

48 48 Aplastic Anemia Acquired (infections, drugs, toxins) or congenital causes (Fanconi, TAR Sx, etc) Acquired (infections, drugs, toxins) or congenital causes (Fanconi, TAR Sx, etc) MR MR  Classic description  Diffuse fat replacement of marrow  Foci of low T1 signal may represent  Residual islands of red marrow  Post Rx regenerative marrow  Development of MDS/Leukemia

49 49

50 50 Pre RxCourse 1Course 2 Foci of low T1 signal may represent Residual islands of red marrowResidual islands of red marrow Post Rx regenerative marrowPost Rx regenerative marrow Development of MDS/LeukemiaDevelopment of MDS/Leukemia

51 51 Radiation Acute and Chronic induced changes Acute and Chronic induced changes MR appearance of radiated marrow depends on phase in which it was imaged and dose MR appearance of radiated marrow depends on phase in which it was imaged and dose  1 st 2 weeks: Increased STIR with slight increase in T1  3 rd -6 th weeks: heterogeneous signal  >6 th weeks: chronic changes of fat replacement  Dose < 30 Gy may have regeneration after 1 year  Dose >30-40 Gy irreversible changes

52 52 Stevens et al. AJR. 1990; 154:

53 53

54 54 Marrow Vascular and Miscellaneous Abnormalities Vascular Vascular  Hyperemia and Ischemia  Transient and regional migratory osteoporosis  RSD  Osteonecrosis  Trauma  Infection  Tumors  Joint abnormalities (degenerative or neuropathic arthropathy) Other Other  Storage diseases: Glycogen (Gaucher’s) or Iron  Paget’s disease  Osteopetrosis

55 55 Transient Osteoporosis of the Hip Painful process that affects mainly young and middle age men in either hip or pregnant women more commonly in the left hip Painful process that affects mainly young and middle age men in either hip or pregnant women more commonly in the left hip Osteoporosis can be severe enough to cause an insufficiency fracture Osteoporosis can be severe enough to cause an insufficiency fracture MR MR  Homogeneous Focal/Diffuse well marginated edema  May spare medial and/or lateral margins of femoral head +/- greater trochanter  Occasional acetabular edema  Small-moderate joint effusion

56 56 Transient Osteoporosis of the Hip

57 57 Regional Migratory Osteoporosis Similar MRI and clinical features as TOH Similar MRI and clinical features as TOH Not confined to the hip and migratory in nature Not confined to the hip and migratory in nature Subchondral regions of the knee, ankle, and hip each may be affected in turn Subchondral regions of the knee, ankle, and hip each may be affected in turn

58 58

59 59 Marrow Ischemia (Osteonecrosis) Synonymous terms Synonymous terms  AVN (Focal lesions in the epiphyses)  Bone infarct ( Metaphysis or diaphysis) Causes Causes  Trauma, steroids, HbS, SLE, Gaucher disease, ETOH, pancreatitis, and idiopathic

60 60 Lonergan, G. J. et al. Radiographics 2001;21:

61 61 Gaucher Disease Rare lysosomal storage disease leading to the accumulation of glucocerebroside within the RES Rare lysosomal storage disease leading to the accumulation of glucocerebroside within the RES MR MR  Focal/Diffuse hypointensity on T1 and T2  Active disease hyperintense on T2 FS and STIR  Lumbar spine involved first followed by appendicular skeleton

62 62 Gaucher Disease Treatment includes administration of the deficient enzyme Treatment includes administration of the deficient enzyme MRI can be used to monitor treatment demonstrating decreased marrow infiltration on serial exams in those who are responding MRI can be used to monitor treatment demonstrating decreased marrow infiltration on serial exams in those who are responding

63 63 Summary Bone marrow disorders have a nonspecific MR appearance but remembering the categories of diseases and correlating this with clinical history can be helpful Bone marrow disorders have a nonspecific MR appearance but remembering the categories of diseases and correlating this with clinical history can be helpful  Marrow Proliferative  Marrow Replacement  Marrow Depletion  Vascular/Miscellaneous Two useful characteristics for evaluating marrow disorders Two useful characteristics for evaluating marrow disorders  Distribution  Normal marrow conversion and reconversion patterns  Signal Intensity (muscle and disc serve as internal standard)  Normal marrow: same or higher signal  Abnormal marrow: lower signal

64 64 References Clinical Magnetic Resonance Imaging, Edelman et al, Clinical Magnetic Resonance Imaging, Edelman et al, Bone and Joint Disorders, Resnick et al, 2005 Bone and Joint Disorders, Resnick et al, 2005 Moore et al. Red and Yellow Marrow in the femur: age related changes in appearance at MR Imaging. Radiology 175: , Moore et al. Red and Yellow Marrow in the femur: age related changes in appearance at MR Imaging. Radiology 175: , Vande Berg et al.: Classification and detection of bone marrow lesions with magnetic resonance imaging. Skeletal Radiology 27: , Vande Berg et al.: Classification and detection of bone marrow lesions with magnetic resonance imaging. Skeletal Radiology 27: , Vande Berg et al.: Magnetic Resonance Imaging of the bone marrow in hematologic malignancies. Eur Radiology 8: , Vande Berg et al.: Magnetic Resonance Imaging of the bone marrow in hematologic malignancies. Eur Radiology 8: , Parisi et al.: Complication of cancer therapy in children: A radiologist’s guide. Radiographics 19: , Parisi et al.: Complication of cancer therapy in children: A radiologist’s guide. Radiographics 19: , Kaplan et al: Bone marrow patterns in aplastic anemia observations with 1.5T MR imaging. Radiology 164: , Kaplan et al: Bone marrow patterns in aplastic anemia observations with 1.5T MR imaging. Radiology 164: , Kaplan et al: Polycythemia Vera and Myelofibrosis:correlation of MR, clinical, and laboratory findings, Radiology 183: , Kaplan et al: Polycythemia Vera and Myelofibrosis:correlation of MR, clinical, and laboratory findings, Radiology 183: , Avila et al.: Mastocytosis: magnetic resonance imaging patterns of bone marrow disease, Skeletal Radiology 27: , Avila et al.: Mastocytosis: magnetic resonance imaging patterns of bone marrow disease, Skeletal Radiology 27: , Stacy E. Smith et al. From the Archives of the AFIP: Radiologic Spectrum of Paget Disease of Bone and Its Complications with Pathologic Correlation. RadioGraphics 2002; 22: Stacy E. Smith et al. From the Archives of the AFIP: Radiologic Spectrum of Paget Disease of Bone and Its Complications with Pathologic Correlation. RadioGraphics 2002; 22: 1191.


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