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Figure 2:The T1-weighted sagittal sequence demonstrates diffusely reduced signal of the bone marrow.
Figure 3:The T2-weighted fast spin echo sequence is relatively insensitive to the abnormal marrow, and is largely unremarkable.
Figure 4:A T1-weighted axial sequence allows comparison of marrow signal with paraspinal muscles. Diffuse bone marrow disorder which in this case led to an eventual diagnosis of Chronic Myelogenous Leukemia (CML). This patient exhibits a diffusely abnormal bone marrow pattern due to previously unrecognized leukemia.
Bone marrow can be essentially divided into three parts: red marrow, yellow marrow and supporting structures such as trabecular bone and reticulum.
Since marrow is not a homogeneous tissue and changes with age, one should expect that its MR appearance will vary depending on the relative proportion of red and yellow marrow, cellularity and density of trabecular bone in the spine and on the type of sequence used for the acquisition. Fat has short T1 and T2 relaxation times and is hyperintense on T1w sequences and hypointense on true (conventional) T2-weighted sequences.
Figure 8:T1w sagittal image demonstrates a poorly circumscribed central area of low signal intensity (arrows) which might mimic a pathologic lesion in this adult male.
Figure 9:In the same patient, a T2w image with fat saturation fails to demonstrate an intraosseous lesion. The T2w FSE sequence is substantially less reliable in assessing spinal marrow, particularly in diffuse disease, as comparison with adjacent normal tissues is more variable than on T1w images13. Other imaging techniques have been utilized in attempts to differentiate normal from abnormal marrow but are not in clinical use on a day to day basis and are beyond the scope of this article. Figure 10:A T1w sagittal image in a teenage boy demonstrates the Ricci pattern 1 with central fat visible along basivertebral veins. Figure 11:Ricci Pattern 1 in a 40 year old man demonstrates only a tiny amount of yellow marrow visible along the basivertebral veins (arrows). Figure 12:This T1w sagittal image demonstrates the Ricci Pattern 3 consisting of a speckled marrow pattern in a normal elderly woman. Figure 13:This T1w sagittal image in an elderly woman demonstrates normal marrow with large round areas of yellow marrow consistent with Ricci pattern 4. Adult marrow does not appreciably enhance to visual inspection after intravenous gadolinium contrast is administered.
Physiologic demand for more mature blood cells (especially red blood cells) beyond the body’s normal capacity to produce them acts to reverse the normal pattern of conversion of red marrow to yellow marrow. Polycythemia vera is characterized by a proliferation of a clone of pluripotent erythrocytotic stem cells. After successful bone marrow transplantation, hematopoietically active stem cells repopulate the bone marrow in a predictable pattern which has been described by Stevens, et al.30.
Marrow replacement disorders are exemplified by proliferation of abnormal (usually malignant) cells in the bone marrow. The classic example of diffuse replacement is the leukemias, a variety of myeloproliferative disorders which have similar appearances on MR.
It is useful to discuss the appearance of post-treatment myeloma on MR as a bridge to understanding the difficulty in providing a clinically useful interpretation of a scan. Figure 20:These MRI findings led to a new diagnosis of lymphoma in an 89 year old man with an unusual display of signal abnormalities likely related to a mixture of pathologies. Bone marrow involvement by malignant lymphoma is much more common with Non-Hodgkin disease than Hodgkin disease and spreads to the marrow 95% of the time hematogenously. Myeloid depletion equates to loss of normal red marrow and thus diffusely markedly fatty signal on all pulse sequences.
Aplastic anemia is manifested as pancytopenia with numerous causes such as viral infection, drug toxicities and as autoimmune responses to malignancies, although most cases are idiopathic. Figure 21:The homogenously and intensely bright signal on T1w images in this 69 year old woman is compatible with a marrow depletion disorder. Figure 22:Bone marrow depletion sharply delineated by the radiation portal in this 52 year old man.
I will just focus on a few of these disorders excluding primary metabolic diseases of bone. One of the manifestations of HIV infections is a pattern of diffuse loss of signal on T1w and T2w images within spinal marrow46. Primary Myelofibrosis, also called myeloid metaplasia, is a rare myeloproliferative disorder of hematopoietic progenitor cells.
Gaucher’s disease is the most common lysosomal storage disorder and can be included in disturbances of the marrow reticulum.
7 Alyas F, Saifuddin A, Connell D: MR Imaging Evaluation of the Bone Marrow and Marrow Infiltrative Disorders of the Lumbar Spine.
8 Tall MA, Thompson AK, Vertinsky T, Palka PS: MR Imaging of the Spinal Bone Marrow Magnetic Resonance Imaging Clinics of North America. 26 Fletcher BD, Wall JE, Hanna SL: Effect of hematopoietic growth factors on MR images of bone marrow in children undergoing chemotherapy. The marrow signal is not brighter than the intervertebral discs, as it should be at this age.
Other diffuse marrow diseases and conditions are possible based on the images and will be discussed. In adults spinal bone marrow is best imaged with MRI due to the exquisite contrast differentiation between normal marrow and pathologic infiltration on many pulse sequences. Marrow signal is similar or even less than adjacent muscle and disc such that pathologic marrow may be very difficult to ascertain6.
However, newer fast spin echo acquisitions (FSE) do not take advantage of this fact in a trade off for speed so that fat is not as hypointense on the T2wFSE most commonly performed today.
A T1w sagittal image demonstrates generally low marrow signal and relatively poor differentiation of marrow from disc. This focus also demonstrates a bull's eye sign where a tiny focus of fat is surrounded by lower signal red marrow. Ricci has described several patterns of normal red marrow and yellow marrow dispersion in the spine after the perinatal period. The first two categories could even be further simplified into Replacement (Proliferative) Disorders with either normal or abnormal cells.
This stimulated growth of hematopoietically active marrow increases the visibility of red marrow in the axial and appendicular skeleton. Erythroid hyperplasia expands the marrow space and thins trabeculae, weakening bone and contributing to the classic endplate deformity. The T1w sagittal image demonstrates diffusely low signal within marrow, not only within the spine but also within the clivus. A T1w sagittal image demonstrates heterogeneous marrow that is generally reduced in signal. This leads to hypercellularity of the marrow which is effectively indistinguishable from a reconversion phenomenon or diffuse marrow replacement by other hematologic malignancies on MR. A few weeks after the transplant, a band-like zone becomes visible in the periphery of the vertebral centrum particularly beneath the endplates. The normal marrow signal usually is completely replaced by abnormal signal best appreciated as low signal on T1w images. Multiple myeloma on MR may appear normal, diffusely abnormal (17a,18a,19a), variegated, multi-focally abnormal or as a solitary lesion (plasmacytoma).
Vertebral body fractures occur frequently in myeloma and certainly retropulsion of bone and compression of neural elements are important and easy things to assess. Bone marrow involvement upstages the patient and may have prognostic and therapeutic implications. This woman had undergone chemotherapy, but the pattern can not be differentiated from aplastic anemia by MR imaging. This finding was reported by Geremia47 in all eleven patients studied and by Steinbach in all 7 of her patients who underwent spinal MR48. A T2w sagittal also demonstrates very low marrow signal compatible with hemosiderosis in anemia of chronic disease.



These cells stimulate the abnormal formation of marrow fibroblasts and incite the release of collagen.
This inborn error of metabolism leads to accumulation of glucocerebrosides within the macrophage-monocyte cell line. Opportunities for such evaluation abound as portions of the marrow can be evaluated on nearly every MR study performed. Water fraction of lumbar vertebral bone marrow estimated from chemical shift misregistration on MR imaging: normal variations with age and sex. Normal variants and frequent marrow alterations that simulate bone marrow lesions at MR imaging. Benign and Malignant Processes: Normal values and Differentiation with Chemical Shift MR Imaging in Vertebral Marrow.
Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy.
MR imaging characteristics of cranial bone marrow in adult patients with underlying systemic disorders compared with healthy control subjects.
Effect of granulocyte-stimulating factors on marrow of adult patients with musculoskeletal malignancies: incidence and MRI findings. Magnetic resonance imaging for the detection of bone marrow involvement in malignant lymphoma.
Effect of radiation therapy on thoracic and lumbar bone marrow: evaluation with MR imaging.
In adults with normal marrow, the marrow should have higher T1-weighted signal than muscle. Such differentiation is better than x-ray, CT, PET, or even radionuclide bone scan with technetium. Red marrow exhibits intermediate signal and tends toward slightly higher or equal signal compared to muscle on both T1w and T2w sequences. Water has a much longer relaxation time compared to fat and is hypointense on T1w and hyperintense on T2w images.
However some fat is seen centrally along the basivertebral veins (arrows) even at this very young age.
Even at this very young age substantial conversion to yellow marrow is displayed in the iliac bones (arrows).
It is important to note that the introduction of each of these special techniques has met with some success and some disappointment. There is great variability among patients and some differences in the patterns between the cervical, thoracic and lumbar segments. Enhancement does occur in pathologic marrow and this difference can be highlighted using post contrast T1w images with fat saturation7. Many diffuse pathologic processes in the spinal marrow have a non-specific appearance with reduced signal on T1w images and intermediate T2w signal.
The focal pattern is the classical pattern of metastases from solid organ malignancies and will not be discussed in this review. Such an observation is problematic in very young children due to the high percentage of hematopoietically active marrow. A mild fracture is present at L1 (arrow) which does not exhibit substantially different signal than that in other marrow. The fracture of T12 (short arrows) looks superficially benign on T1w images (20a) but has abnormal signal on T2w (Fig 20b) and STIR (20c). Marrow depletion to at least some degree is common after radiation therapy and chemotherapy (21a, 22a) and can be severe enough to notice on MR.
It is interesting that after bone marrow ablation, stem cell transplantation and marrow regeneration, a typical pattern of reconversion is found beginning in bands along the endplates.
This find is felt secondary to hemosiderosis, excessive iron accumulation in marrow macrophages which is histologically characteristic of anemia of chronic disease (23a,24a). Secondary myelofibrosis is much more common, usually resulting from chemotherapy or radiation therapy. These so called Gaucher cells replace the normal marrow leading to decreased T1w and T2w signal similar to so many other reconversion and replacement disorders5.
Knowledge of the signal on the variety of pulse sequences and pattern of marrow in the normal spine is essential knowledge in deciding what is potentially pathologic and what is not.
The imaging findings are such that the radiologist feels compelled to place a telephone call to the referring physician. In the adult red marrow is concentrated in the axial skeleton, but may be focally scattered in other parts of the skeleton. This process begins first and is most evident in the appendicular skeleton and proceeds in a centripetal manner (5a,6a,7a). Since red marrow has a mixture of water, fat and protein it exhibits intermediate signal intensity on both T1w and T2w sequences1,7,8,9. Pattern 1 begins in younger patients where central fat is visible along the basivertebral veins. STIR images or post contrast images may or may not differentiate red marrow hyperplasia from pathologic cellular replacement. Typically this process occurs in a reverse direction from central to peripheral as demands increase.
A T1w axial image (14c) demonstrates that marrow signal in sacrum and iliac bones is lower than that of adjacent muscle.
Although reports have suggested that clival marrow signal changes are useful in differentiating a benign reconversion process from a more serious replacement (e.g. There are likely several factors contributing to the marrow appearance including: administration of recombinant erythropoietin, myelofibrosis, iron overload, secondary hyperparathyroidism and aluminum accumulation.
An abnormality may not be evident on T2w FSE but often is of greater than normal signal on STIR or T2w fatsat. It is curious that some areas suggesting degenerative fat persist (arrowheads) despite complete marrow replacement otherwise.
The development or progression of fractures does not necessarily point to progression of disease as tumor elimination may be followed by loss of structural support. In the first few days after initiating radiation, the effects are dominated by necrosis, edema and hemorrhage, especially on STIR.
In this form of anemia impaired release of iron from macrophages contributes to impaired utilization of iron for hemoglobin production. Primary myelofibrosis is also a myelodysplasia and therefore predisposes to conversion to leukemia. The conversion of normal red marrow to yellow marrow and the reconversion back to hematopoietically active marrow under physiologic stress is a common occurrence but highlights one weakness of MR, its lack of specificity without clinical information.
The most common pathologic infiltration of marrow is metastases from solid organ tumors, but since metastatic disease is much more often multifocal than diffuse in its imaging pattern in the spine, it will only be briefly discussed in this article.
Yellow marrow is generally hematopoietically inactive and is concentrated in the adult in the appendicular skeleton. Importantly, the intensity of marrow in an adult comes with an internal control when viewing T1w sequences. Visibility can be augmented by suppressing the fat which is present in both red and yellow marrow.
Examples of this physiologic stress include demands on an endurance athlete, particularly training at high altitude22, and cigarette smokers, especially obese women23.
Histologically this band of intermediate signal is composed of hematopoietically active cells. The multi-focal pattern is the most common pattern and mimics solid organ metastases to the spine. The long arrow connotes a slightly hypointense poorly defined lesion on T1w (20a) which is quite conspicuous on the T2w (20b) and STIR (20c) that is typical for focal tumor except in its lack of defined borders on the T1w view. Beginning approximately 3-6 weeks after initiating radiation therapy, the marrow signal begins to increase on T1w images both qualitatively and quantitatively. Hemosiderosis can occur in a variety of other disorders such as hemolytic anemias, hemochromatosis and some malignancies.


Some authors describe the MR appearance of myelofibrosis as very low signal on T1w and T2w images, while others do not.
In a patient such as the test case who demonstrates diffusely low T1w marrow signal on MR, the differential diagnosis is long and includes many benign reconversion conditions, malignant myeloproliferative disorders and abnormalities of the supporting reticulum.
Marrow content and its distribution in the body changes substantially with age and differs by sex1,2,3,4.
Except for the sternum, ribs, proximal aspects of the extremities, and the pelvis, the overwhelming majority of red marrow is in the spine in an adult1,7. On T1w images in the adult, the signal of the vertebral body should be higher than adjacent intervertebral discs or muscle with few exceptions10,11. Only a minority of patients with chronic renal failure have spinal marrow with this appearance.
Up to 30% of focal myeloma lesions visible on T1w studies are not distinct on T2w images but may be visible on T2w fatsat or STIR images. Hemorrhages may occur within a vertebral body raising the T1w signal which might under some circumstances confuse the evaluation of a segment.
Arrowheads denotes a lesion which has some bright T1w signal that appears substantially larger on the T2w and STIR images, possibly representing a hemorrhagic metastasis. A significant percentage of patients with this disorder progress to myelodysplasia and eventually leukemia, if they do not undergo bone marrow transplantation. Plasma cell proliferation in marrow is also well known in HIV and may contribute to the marrow appearance49. This discrepancy is likely due to the degree of fibrosis present, whether the fibrosis is primary or secondary, and whether the primary form is in a preleukemic state7,25,28,50. However, there is a variable mixture of red and yellow marrow in the spine beyond infancy with progressive increase in fat content of red marrow and increased proportion of yellow marrow with aging2,3. Exceptions include calcified discs which have bright T1w signal and particularly islands of red marrow which can be confused with focal pathology such as tumor (8a,9a). Dixon fat saturation techniques usually nullify the signal from fat by a pre-saturation pulse. Pattern 3 (12a) can be referred to as a speckled pattern with tiny foci of interspersed red and yellow marrow. Hyperplastic marrow does not differ greatly from a diffuse replacement disorder, sharing T1w characteristics of being iso- or hypointense to muscle. Moulopoulos reported that in their experience the marrow repopulation gradually becomes more homogeneous over time25. A large number of studies have been performed to assess the usefulness of various advanced MR techniques in diagnosing and following patients with leukemia. The diffuse pattern mimics other replacement disorders such as leukemia and even marrow reconversion.
Asterisks denote a larger central area which appears normal on the T1w images but clearly abnormal on the T2w and STIR views. The recovery of normal red marrow signal has been reported both as patchy and peripheral band-like with band-like recovery apparently more common in the young. These observations plus the fact that reconversion tends to be focal has contributed to some MR descriptions of aplastic anemia as heterogeneous.
The more yellow marrow which is present within a vertebral body the more homogeneously suppressed (hypointense) the body will appear with these techniques. Pattern 4 (13a) is exemplified by larger, rounder areas of yellow marrow and poorly defined areas of red marrow.
T2w fatsat, STIR and post enhancement characteristics will differ in most but not all cases. The variegated pattern occurs in less than 5% of patients and is not only attributable to tiny clusters of plasma cells but to inhibition of hematopoiesis creating tiny foci of fat.
Chemotherapy and radiation therapy change the marrow in predictable ways and may affect its appearance on MR. For doses greater than 30-40 Gy, the marrow changes are permanent due to ablation of vascular sinusoids.
Most pathology will demonstrate relatively higher signal on T2w fatsat or STIR than red or yellow marrow. Except for transition from an infantile pattern of homogeneous red marrow to pattern 1, the patterns do not progress or evolve in a predictable or clinically useful manner3. In hyperplastic anemias iron accumulation in marrow macrophages related to transfusions or hemolysis may contribute to reduced marrow signal7,8,13,24,25,26,27.
Around 50% of patients with focal or diffuse MR patterns do not have lytic lesions on conventional x-rays. Initially edema and necrosis occur which can be followed by hypocelluarity if a positive tumoral response is elicited.
Most of the vertebral bodies have much less high T1w signal within them than normally seen in an 89 year old person. Images obtained with these sequences tend to be grainier and less distinct due to suppression of signal from lipid protons decreasing the signal to noise ratio9. The patterns may seem to overlap in clinical practice but their descriptions are a useful teaching tool. The use of MR has impacted the staging and follow-up of patients with myeloma and has led to a modification of the classic Durie and Salmon staging system. Often realization that the marrow is depleted is obvious only after observing uninvolved areas of the spine7,25,42,43. Red marrow is composed of 60% hematopoietically active cells in the young but only about 30% in the elderly5. It has been discovered that patients with a normal or variegated bone marrow appearance tend to Stage I disease. About two weeks later fatty replacement begins and may be visible on MR and classically occurs around the basivertebral veins.
This subjective assessment can be more accurate at qualifying marrow within bone as normal or abnormal than certain quantifying methods20. However some focal lesions in myeloma do not change significantly in appearance for up to 5 years. Thankfully, this perceptual averaging becomes easier as the patient ages and the percentage of fat within the marrow increases. Reconversion can occur depending on the degree to which the therapy has obliterated the marrow.
Additionally, bone trabeculae decrease signal in the vertebral body by creating local field inhomogeneities. Bone marrow reconversion and the diffuse pattern of myeloma may be similar especially if bone marrow stimulators have been administered.
This may contribute to the observation that marrow signal can be very high in elderly women on T1w images, whose trabeculae may thin from osteoporosis. Studies have shown that a pre-treatment intensely, diffusely enhancing focal lesion which does not enhance post-treatment is inactive. Partially or peripherally enhancing lesions are non-specific as post-treatment fibrosis will enhance7,8,25,36,37,39,40.
It is interesting that some authors emphasize the STIR and post-contrast differences in appearance between hyperplastic red marrow and malignant infiltration while others do not. I think this relates not only to the variability of pathology affecting marrow but also that the best discrimination after enhancement is obtained through quantitative measurements in the first minute after a dynamic infusion of contrast, something which is not usually performed in day to day practice.
Clearly, to interpret a follow-up MR in a patient with a spinal marrow replacement disorder is potentially a complicated task (20a,20b,20c).




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