To understand physiological and pathological changes that occurs to BM, you have to be aware first with normal BM anatomy and the function of its components.

The BM consists of 3 components:

1.     Trabecular bone

2.     Red marrow

3.     Yellow Marrow

 

Trabecular Bone:

It is formed of bridging trabeculae, which forms the framework that supports both red and yellow marrow.

 

Red marrow:

It is also called cellular, active, myeloid and hematopoietic marrow.

It is composed mainly of different cellular elements (60% of its component) and is characterized by having rich sinusoidal vascular supply.

 

Yellow marrow:

It is also called fatty and in active marrow.

They provide the surface for nutritional support to red marrow.

It is composed mainly of fat (80% of its component) and is characterized by having sparse vascular supply.

 

At birth, nearly the entire osseous skeleton is formed of red marrow. Then, conversion from red to yellow marrow occurs over the following 2 decades to be generally completed by 25–30 years of age.

Conversion starts at the extremities and proceed to distal bones; starting in feet and hands then progress to humeri and femora.

Within each long bone conversion occurs with the following sequences: (Fig.1) 

·        Epiphyses and apophyses.

·        Diaphysis

·        Distal metaphysis

·        Finally; proximal metaphysis.

 

In adults, red marrow represents only half the marrow content and it is located predominantly in the axial skeleton and proximal limbs.

 

 

The reverse of this process can occur with the yellow marrow being reconverted to red marrow when there is increased hematopoietic demand. This reconversion occurs in the exact reverse sequence of conversion; called reconversion.  

 

 

MRI appearance of normal bone marrow:

 

T1-weighted spin-echo sequences are the most useful for evaluating bone marrow. T2 and STIR weighted images are also commonly used.

Normal MRI appearance can be simplified in the following table:

 

	T1 WI	T2 WI	STIR	NOTES
Yellow Marrow	High SI	Iso SI	Low SI	Resembles subcutaneous tissue fat in all sequences.
Red Marrow	Iso SI	Iso SI	Iso SI	Higher SI than normal muscle and intervening discs on T1 WIs

 

SI: signal intensity.

Iso SI: intermediate SI.

 

 

WHENEVER RED MARROW BECOMES EQUAL OR LOWER IN SI THAN NORMAL DISCS AND MUSCLES ON T1WIS, PATHOLOGY IS CERTAINLY PRESENT.

 

 

It’s crucial to differentiate isolated focal are of red marrow from pathological lesions as metastasis.

This is done by knowing the fact that neoplasm totally replaces normal marrow, while red marrow will always have fat cells scattered throughout it, this is done by in and out of phase gradient echo sequences, we will find that:

 

	In phase	Out of phase
Red Marrow	High SI	Low SI
Neoplasm	High SI	High SI

(Not specific for early cases because if we have low tumor burden, it won’t replace the whole BM, and we will have some fat cells)

 

Marrow Pathology:

BM abnormalities are usually nonspecific, even normal appearance of BM doesn’t eliminate the possibility of having significant BM disease, making it almost impossible to reach specific diagnosis, that’s why a systemic approach is used to limit our differential diagnosis by classifying BM abnormality into 5 main different categories: (Fig. 2)

1.      Proliferative marrow disorder.

2.      Replacement marrow disorder.

3.      Marrow depletion.

4.      Vascular abnormalities.

5.      Miscellaneous marrow disease.

 

1.      Marrow proliferative disorders:

 

It’s a category that arises from proliferation of cells that normally exist in BM, it can be furtherly categorized into benign and malignant diseases.

Generally, this category affects BM diffusely rather than focal lesions.

Benign disease:

·        Myelofibrosis

·        Myelodyspalstic syndrome

·        Polycythemia rubra vera

·        Mastocystosis

·        Reconversion from yellow to red marrow

Malignant disease:

·        Leukemia

·        Multiple myloma

·        Primary amyloid

·        Waldenstom’s macrogubinemia

 

For proliferative marrow disorders, the major MRI abnormalities that are identified are:

Abnormal SI.

Abnormal distribution of normal red marrow SI.

 

Both abnormal distribution and SI.

A common pitfall in assessing BM is assessing it in FSE sequences as both fat and water will elicit high SI, therefore the signal of the BM lesion will blend with the background hematopoietic marrow.

 

Reconversion from yellow to red marrow

This occurs when the individual's demand for hematopoiesies increases. Either due to marrow replacement disorders, severe anemia, increase oxygen requirement as in high level athletes and high attitude or in obese females; which is mostly the most common cause of marrow reconversion in MRI.

It occurs exactly in a reverse sequence in which conversion from red to yellow marrow occurred during normal maturation.

Features indicating marrow reconversion on MR images are:

• symmetry of changes with low signal intensity on T1-weighted images.
•  changes do not extend beyond the growth plate line, sparing the articular ends.
•  changes have characteristic location in relation to the axial skeleton.

 

Mastocytosis and myelofibrosis:

Both conditions stimulate fibrosis of the reticulin of the marrow with sclerosis of the trabecular bone resulting in low SI in all pulse sequences.

This can also occur in patients with hemolysis due to hemosiderosis which cause diffuse low SI.

 

Monoclonal Gammopathies:

It’s a disease that is categorized according to its severity. It is divided into 2 main groups, aggressive monoclonal Gammopathies and nonmyelomatous monoclonal Gammopathies. 

MRI has shown a valuable role in predicting which patients are likely to have disease progression, with abnormalities that consist with diffuse or focal marrow lesions in the spine or pelvis

 

¤Malignant:

 

Leukemia:

It usually presents by focal, or more commonly diffuse abnormalities in the metaphysic and diaphyses.

In advanced leukemic patients abnormal SI can be attributed to either large tumor burden or due to marrow hyperplasia as a compensatory mechanism by the body trying to replace infiltrated BM elsewhere.

• T1 WI: Low SI, less than muscles and disks
• T2 WI: High T2, due to high water content of leukemic cells.

 

Aggressive monoclonal Gammopathies:

Multiple myeloma, primary amyloidosis and Waldenstrom’s macroglobulinmia are very similar to one another having identical MRI features.

One special feature to Waldenstrom’s macroglobulinmia will be bone infarction which occurs as a result of hypervascular states.

Multiple myloma is a common disease that can have different MR imaging features according to the severity of the disease.

The MRI patterns in order of increasing severity are:

 

1.     Normal marrow pattern.
2.     Focal lesions.
3.     Variegated appearance
4.     Homogenous diffuse pattern.

 

It has variable appearance on both T1 and T2 WIs, making it hard to diagnose.

 

• T1WI: the lesion can be hypointense as any suspicious BM lesion, or it can by hyperintesnse due to intralesional hemorrhage.
• T2WI: the lesions may be high or low in approximately 50% of newly diagnosed patients.

 

 

Non common specific appearance of multiple myeloma:

• Mini-brain appearance: this occurs in focal lesions when bone radiates inwards from the focal margins of the lesion resembling sulci and gyri.
• Variegated appearance: multiple small low SI foci on T1 WIs, resembling the appearance of sprinkled black pepper on the bone marrow (specific)*

 

NB:

• Post chemotherapy treatment hyperintense BM lesions on T2 WIs become hypointense, Hence, it is important to preform pre and post treatment MRI exams, as this finding have no significance in 50% of patients who already have low T2 SI lesions prior treatment.
• Alternatively, Contrast can be used to evaluate treatment response showing no contrast enhancement or conversion of the enhancing pattern to less severe form.

 

MR examination is performed in this spectrum of diseases to direct the biopsy and to monitor treatment response, not for initial diagnosis as they all resemble the same radiological features.

 

 

2. Marrow replacement disorders:

 

it’s a spectrum of diseases characterized by replacing the BM with cells other than those inherit in it.

It differs from marrow proliferative disorders in resembling focal patterns more than diffuse ones.

The main diseases within this spectrum are:

• Metastatic diseases
• Lymphoma
• Primary bony tumors
• Osteomyelitis

 

Metastatic disease: (Fig 4, Fig 5)

MRI is sensitive in detecting metastasis and monitor treatment response. Typically presents as a focal area of:

• T1WI: low SI
• T2 WI: High SI

 

Halo signs:

• A focal lesion surrounded by a halo of high SI edema on T2 WI, indicating active lesion. “the devil sign”
• A focal lesion surrounded by a halo of high SI yellow marrow on T1 WI, indicating resolving lesion. “the angel sign”

 

Sclerotic metastasis typically appears as low SI in all pulse sequence.

Other common presentation to metastasis is pathological fracture. Considering the fact that both osteoporosis and metastasis are common in old age, it is crucial to differentiate pathological fracture from osteoporotic fracture.

 

	Osteoporotic Fracture	Pathological fracture
Abnormal SI	Limited to vertebral body	Reaching the pedicles and the posterior element.
Soft tissue mass	Absent	Present
Marrow	Some normal fatty marrow are spared	The whole vertebra is involved
Posterior border	Concave	convex
Number	Usually single	Usually multiple
Fracture line	present	Absent
DWI	No restrictions	restricts

If differentiation between both entities failed, follow up with MRI after 8 weeks is recommended for accurate diagnosis.

 

Less commonly metastasis can present by diffuse pattern either homogenous or heterogeneous appearance.

 

Lymphomas:

Non-Hodgkin disease is more commonly to involve the BM than Hodgkin disease. It can represent in various forms as: multi-focal, diffuse or mottled appearing.

It usually has signal intensity resembling metastasis being low in T1WIs and high on T2WIs.

 

Primary bony tumors:

The nature of the lesion is better diagnosed by conventional radiographs and MRI is used for monitoring treatment response.

 

Osteomyelitis:

It refers to infection of the bones.

It presents with signal alteration of the BM, eliciting low SI on T1WIs, high SI on T2WIs with post contrast enhancement of the bone marrow, surrounding abscess margins, periosteum and adjacent soft tissue collections.

 

 

3.Marrow Depletion disorders:

 

Diffuse or regional complete fatty replacement of red marrow with fat on MRI as a consequent of aplastic anemia, chemotherapy and radiotherapy.

It will follow fat signal intensity on all pulse sequences.

 

Aplastic Anemia:

It  can be presented by 2 radiological patterns on MRI, either diffuse fatty changes (homogenous high T1 SI) in un treated cases, or focal areas of red marrow within the yellow marrow in treated cases (eliciting iso SI on T1 WI and slightly high SI on T2WIs).

 

Radiotherapy:

Bone marrow changes due to do irradiation are time and dose dependent.

Early the BM response of to radiation by edema formation. Subsequently, the red marrow disappears within 3-6 weeks post treatment with total depletion of red marrow within 6 weeks, with MR showing homogenous high SI on T1WIs.

 

A  cut off, straight line representing the junction between the normal irradiated BM and the abnormal radiated fatty marrow can be seen.

 

Reconversion can be either homogenous or with peripheral distribution surrounding the vertebral bodies, mimicking tumors.

 

Chemotherapy:

The response to chemotherapy is variable from one patient to another ranging from no signal alteration, BM edema to diffuse fatty marrow.

After session of chemotherapy the BM changes resolve.

 

 

4.Vascular Abnormalities:

This spectrum is divided into two main categories Hyperemia , usually presented by edema and ischemia.

A.   ♦Hyperemia:

There are wide differential diagnosis to BM edema, I can be either due to :

• Trauma. (Fig. 3)
• Transient osteoporosis of the hip
• Regional migratory osteoporosis.
• Reflux sympathetic dystrophy
• Early osteonecrosis
• Infections
• Tumors

They will all be presented with the same BM signal alteration resembling fluid in the form of low SI on T1WI and high SI on T2WI.

They will differ from each other by their pattern, associated findings and clinical history, for example:

In trauma: edema will implicate the opposing aspects of the bone at the site of trauma.

Infection and tumors: there is usually perilesional edema, with the presence of the primary lesion itself.

·       Transient osteoporosis of the hip: (Fig 6)

It is a self-limiting condition that presents spontaneously with sudden-onset pain in the hip, likely associated with  over activity of the sympathetic system.

It affects middle age men and women during the 3rd trimester of pregnancy.

MRI: bone marrow edema pattern implicating the femoral head, neck, and down to the intertrochanteric region.

 

·      Regional migratory osteoporosis:

It resembles exactly transient osteoporosis of the hip, yet with major difference being that the abnormality is seen migratory to involve other regions as knee and ankle, usually with subchondral location.

 

·      Reflux sympathetic dystrophy:

It is similar to the previous 2 entities yet with abnormality implicating area with cast following trauma.

 

 

B.   ♦ Ischemia:

This is synonymous to osteonecrosis resulting from interruption of blood supply, which affects mainly areas with yellow bone marrow due to decreased blood supply.

Early detection of osteonecrosis is critical, as treatments are more successful in early course of the disease.

MRI is the most sensitive means to diagnose osteonecrosis.

Early it represents BM signal alteration resembling edema, then a characteristic low SI serpentine rim is seen in most of cases on both T1 and T2WIs following geographic pattern.

On T2WIs the inner border of the line is seen lined by hyperintense SI forming double-line sign.

 

5.    Miscellaneous:

 

Composed of different diseases that affects the BM, but can’t fit in one category as:

Gaucher’s, Paget’s, osteoptrosis and hemosiderin depoasition.

Each disease has its own appearance with no common features.

 

 

Osteoptrosis:

It is a disease manifested by dedifferentiation between the bone coterx and medulla.

Presented by low SI in all pulse sequences.

 

Paget’s disease:

Its main role is not in diagnosis which is easily seen on conventional radiographs, but it has a superior role  it detecting sarcomatous changes.

 

Hemosidrin deposition:

It occurs in cases of red blood cells breakdown and chronic blood transfusion.

Presented by extremly low SI in all pulse sequences.