Bone Marrow

5.1 Normal Bone Marrow

Bone marrow is divided into two types (with a smooth transition between the two):

• Yellow marrow (fatty marrow) has a high fat content and a poorly developed capillary bed.

• Red marrow (hematopoietic marrow) is composed of a mixture of hematopoietic cells and fat with a highly developed network of sinusoids.

5.1.1 Distribution and Age-dependent Physiological Conversion of Red to Yellow Marrow

Red marrow predominates at birth and is increasingly replaced by fatty marrow with aging This normal process follows a typical distribution pattern:

1. In the peripheral skeleton it proceeds in a distal-to-proximal manner (i.e., the forearm before the upper arm, for example).

2. Within the peripheral bone, this conversion occurs initially in the epiphyses and apophyses, followed by the diaphysis and finally the metaphysis; in turn, the distal metaphysis converts first (even in adults, proximal bones maintain residual hematopoietic marrow; Fig. 5.1).

3. In adults, hematopoietic marrow is still predominantly located in the axial skeleton where gradual fatty conversion of the marrow is a life-long process ( Figs. W5.1 and W5.2).

4. A diagnostically important feature is an (almost) symmetrical distribution at any age.

CT. The distribution of red and yellow marrow may be vaguely discerned from the lower attenuation value of fat (fatty marrow, approximately100 HU; hematopoietic marrow, approximately 50 HU; Fig. 5.2). Any objective measurement based on the trabeculation pattern is very limited and most likely only possible for long tubular bones.

MRI. MRI is best suitable for demonstrating bone marrow composition owing to its high soft-tissue contrast. A high contrast between fat and fluid content may be achieved by using the following sequences:

• Fat appears hyperintense on T1W sequences, while fluid is hypointense.

• Fluid-sensitive fat-saturated sequences (T2W and PDW sequences with fat saturation, inversion recovery with bright fluid and dark fat) produce high contrast between fat and fluid.

• Contrast between fluid and fat is poor on T2W sequences without fat saturation. Fibrosis and sclerosis are hypointense.

• Contrast agent uptake is higher in hematopoietic marrow. It should be noted that the administration of contrast is not reliable for differentiating between diffuse infiltrations and normal red marrow.

Note

A patchy pattern may be evident as a normal variant, with focal nodular hyperplasia (the epiphyses remain uninvolved; Fig. 5.3) or dense pockets of fat in the bone marrow of elderly patients, especially in the spine ( Figs. 5.4 and 5.5). Patchy bone marrow signal alterations in the skeleton of the foot are normal in children between the ages of 4 and 12 years ( Fig. 5.6).

NUC MED. Metabolic activity (e.g., FDG uptake in PET imaging) is somewhat higher in hematopoietic marrow than in fatty marrow.

5.1.2 Reconversion of Yellow to Red Marrow/Bone Marrow Hyperplasia

This process takes place in a direction opposite to that of conversion. Marrow within the proximal portion of a bone is recruited first for hematopoiesis, i.e., the proximal metaphyses in the long tubular bones ( Fig. 5.7). Typically, reconversion does not take place in the epiphyses and apophyses.

Caution

Physiological bone marrow conversion may be delayed in children!

Causes of reconversion

• If the existing hematopoietic marrow is insufficient (e.g., in the presence of fibrosis, cell infiltration), fatty marrow regions are at once recruited for new blood formation.

• Reconversion is also seen in the “healthy”:an increased demand for hematopoietic marrow can exist, for example, in marathon runners and in those taking hematopoietic factors, as well as in smokers and obese patients.

• Compensatory hypertrophy of hematopoietic marrow is seen e.g., in cases of anemia, infection, heart failure, and lung disease.

Fig. 5.1 Normal age-dependent distribution of red and yellow marrow in the femur.

Fig. 5.2 Bone marrow on CT; 1-mm CT slice. The comparison between muscle and bone marrow gives a semiquantitative assessment of the presence of fatty marrow. Fine trabeculae will falsify the measurement of a region of interest.

Fig. 5.3 Nodular hyperplasia of the bone marrow. Normal variant. (a) Nodular red marrow in the surgical neck of the humerus (T1W image). (b) Corresponding PDW image. (c) CT demonstrates a rounded lucency and reduced trabeculae at the site of the MRI finding; no marginal sclerosis.

Fig. 5.4 Female breast cancer patient after chemotherapy. A definite differentiation between red marrow reconversion and tumor infiltration is not possible.

Fig. 5.5 Diffuse, in part nodular, infiltration of the bone marrow by plasmacytoma. Residual hyperintense islands of fat are also seen.

Fig. 5.6 Patchily increased bone marrow signal within the foot of a 12-year-old child. Normal variant.

Fig. 5.7 Symmetrical residual hematopoietic marrow in the proximal femurs in this 40-year-old obese female smoker.

Note

In order to better evaluate diffuse alterations of the bone marrow, T1W contrast may be compared with normal skeletal muscle or, in the spine, with the signal of the intervertebral disks. Bone marrow that is darker than skeletal muscle or disk is an indication of diffuse marrow infiltration, which is usually pathologic. This is also referred to in the spine as the “bright disk sign” ( Figs. 5.8 and W5.3).

5.2 Anemias and Hemoglobinopathies

5.2.1 Anemias

Pathology. Anemias develop from abnormal blood loss (acute or chronic hemorrhage), reduced production (e.g., aplastic anemia; deficiency of iron, vitamin B₁₂, or folic acid; erythropoietin deficiency), ineffective hematopoiesis (hemoglobinopathies), and increased degradation (e.g., hemolytic anemia).

Aplastic Anemia

Pathology. This is a rare disorder. Aplastic anemia is associated with inadequate blood-cell formation within the bone marrow and blood. There can be a number of causes for this, such as radiotherapy, chemotherapy, paroxysmal nocturnal hemoglobinuria, Fanconi anemia, hepatitis, pregnancy, and thymoma. However, aplastic anemia may also be idiopathic.

MRI. There are signs of cellular depletion as evidenced by extensive fatty marrow. Hematopoietic marrow is once again identified after successful therapy, appearing as diffuse or patchy islands of cellular marrow. Hemosiderosis (Chapter 5.3.1) may develop after multiple blood transfusions.

5.2.2 Hemoglobinopathies (Thalassemia, Sickle Cell Anemia)

Pathology. All hemoglobinopathies have a similar effect on the skeletal system and result in alterations of bone and bone marrow that are the result of bone marrow hyperplasia due to insufficient hemoglobin production.

Radiography. Expansion of the medullary cavity, coarsened trabeculation, and cortical thinning are typical radiographic signs. The so-called hair-on-end phenomenon is seen on skull radiographs ( Fig. 5.9). “Fish vertebrae” occur in the spine secondary to decreased bone density.

MRI. MRI will demonstrate reconversion of bone marrow or—in children and adolescents—delayed fatty marrow conversion. Extramedullary blood production may develop, producing typical symmetrical, lobulated, paravertebral and presacral space-occupying lesions that have intermediate signal intensity on T1W images and enhance moderately with contrast ( Fig. W5.4).

Acute and chronic complications involving bone are mainly the result of vascular occlusion, infection, or a combination of the two.

Vascular occlusion. In the growing skeleton, this results in a disturbance of bone growth due to premature closure of the growth plates (H-shaped vertebra; Fig. 5.10). Infarctions occur in all regions of the tubular bones ( Fig. 5.11) and less commonly in flat bones. Infarction may also occur in muscles and other soft tissues.

Osteomyelitis. Osteomyelitis is commonly caused by Staphylococcus aureus or Salmonella typhi. It is usually not possible to discriminate between septic infarction (osteomyelitis) and aseptic infarction.

5.3 Metabolic Bone Marrow Alterations

5.3.1 Hemosiderosis and Hemochromatosis

Pathology. Hemochromatosis is a hereditary disorder leading to iron deposition in organs as well as in the bone marrow as a result of excessive iron absorption. “Hemosiderosis” is the more general term for increased iron deposition in tissues, most commonly after multiple blood transfusions, but may also occur secondarily to hemolytic anemia and other disorders.

MRI. Iron deposition renders the bone marrow hypointense on T1W and T2W sequences. T2* GRE sequences demonstrate particularly low signal intensity. An almost complete loss of signal may be seen in marked cases (known as “black marrow”; Fig. 5.12).

5.3.2 Lipidoses and Lysosomal Storage Diseases

These disorders are due to a genetic defect resulting in the accumulation of partially degraded, insoluble metabolites within the lysosomes.

Pathology. One example is Gaucher’s disease (glucocerebrosidosis), in which glucocerebrosides accumulate in the reticuloendothelial cells of liver, spleen, and bone marrow.

Radiography. Typical features include reduced tubulation of long tubular bones (Erlenmeyer flask deformity), osteoporosis (with subsequent fractures), and osteonecrosis (H-shaped vertebrae; see Fig. 5.10). Less commonly seen are sharply marginated or moth-eaten osteolytic lesions and very rarely osteosclerosis.

MRI. The areas of cellular deposition are hypointense, both on T1W and T2W sequences. Initially the signal alteration tends to be patchy. Typically the region around the basivertebral veins still demonstrates normal bone marrow signal in less severe cases. The signal becomes diffusely hypointense in advanced stages. Subsequently, bone marrow recruitment with reconversion takes place. These alterations regress in patients who respond to enzyme replacement therapy.

Fig. 5.8 Bright disk sign due to diffuse hematopoietic marrow in a 74-year-old patient with anemia. Note the hypointensity of the bone marrow compared with the disks (and with the subcutaneous fat).

Fig. 5.9 Thalassemia. (a) Typical hair-on-end appearance of the skull. (b) Coarsened trabeculation and expanded medullary cavities in a child’s hand. (c) Erlenmeyer flask deformity (metaphyseal flaring in long bones).

Fig. 5.10 H-shaped vertebra (also known as Lincoln log vertebra) in sickle cell anemia.

Fig. 5.11 A 25-year-old patient with known sickle cell anemia. Sickle-cell crisis 3 weeks previously; since then pain in the upper arm. (a) Hyperplastic red marrow extending as far as the epiphysis. (b) Extensive infarctions, presumably developed over time, in the proximal diaphysis.