Joint Program in Nuclear Medicine

Bone Marrow Scintigraphy

Chandra Dass, MD 
J. Anthony Parker, MD PhD

February 11, 1997

Presentation

A 65 year old male with non-Hodgkin lymphoma, in relapse after bone marrow transplant, was admitted with acute respiratory distress. Routine blood workup showed thrombocytopenia, which continued to drop even after repeated plasmapheresis. Peripheral smear showed normal white count and normal reticulocyte count and no evidence of microangiopathic changes. A bone marrow aspirate from the iliac crest demonstrated a completely aplastic marrow with no hemopoietic cells. A repeat marrow aspirate from the other iliac crest revealed the same findings. The patient was referred for a Tc-99m sulfur colloid bone marrow scan.

Imaging Findings

Since the bone marrow findings were incompatible with the peripheral blood picture, a sampling error was suspected. The bone marrow scan showed absent marrow in both iliac region. The region of absent activity was rectangular in appearance and was due to prior radiation therapy unknown at the time of biopsy. A repeat biopsy from the sternum was successful and revealed marked erythroid hyperplasia, normal granulocyte maturation and megakaryocyte hypoplasia.

Discussion

During fetal growth, hematopoiesis takes place in all bony cavities (axial and appendicular skeleton) as well as in liver and spleen. Prior to birth, splenic and hepatic hematopoiesis disappear, and gradually thereafter hematopoietic tissue (red marrow) is replaced by fat (yellow marrow) beginning in the distal bones and retracting to the adult pattern by age ten. In the adult, hematopoietic marrow is confined to the axial skeleton and proximal portions of the humerus and femur. Bone marrow weighs approximately 3000 g in normal adult man. The red and yellow marrow each constitute half of the bone marrow weight. However 50% of red marrow is adipose tissue. Therefore, about 75% of total marrow in adults is adipose tissue.

The three major tissue that constitute the red marrow include

The reticuloendothelial cells and the hematopoietic cells provide functional mechanisms for radiopharmaceutical localization in bone marrow scintigraphy.

Radiotracers:

The radiotracers used for bone marrow scintigraphy can be divided according to the target cell type into Fe-52 citrate is physiologically the ideal agent for the assessment of erythropoietic marrow activity. Unfortunately, it is relatively expensive (cyclotron produced) and suboptimal for imaging with the currently widely available gamma cameras (positron emission). However, lack of activity in the liver & spleen allows evaluation of extramedullary hematopoiesis in the above organs and detection of abnormalities in the thoracolumbar spine.

At present, Tc-99m sulfur colloid is the colloid agent most commonly used in the United States. Because of the smaller particle size, sulfur colloid prepared by hydrogen sulphide bubbling technique (< 100 nm) yields better marrow images than prepared by acid reduction of sodium thiosulfate (100-1000 nm). Nanocolloids (Tc-99m-microaggregated human serum albumin; Tc-99m-antimony sulphide colloid) are mainly used in Europe (<80 nm). Except in a few predictable clinical situations (pure red cell aplasia; acute radiation injury; myelosuppressive chemotherapy; treated polycythemia vera; myelofibrosis), scans with Fe-52 and Tc-99m-sulfur colloid show identical marrow distribution pattern, thus allowing the latter to be used as a practical alternative to the former. On the other hand, normal liver and splenic uptake makes colloid technique useless in evaluating extramedullary hematopoiesis in these organs and detection of abnormalities in the adjacent thoracolumbar spine.

Though In-111 binds to transferrin in exactly the same manner as iron, the biological behavior of indium and iron is different (In-3+ is not reduced like iron to In-2+ state) in as many respects as they are similar, and marrow In-111 uptake can only be extrapolated to the distribution of erythropoietic marrow with great care. The mechanism of marrow uptake is not yet clear, though in patients with normal bone marrow the distribution is similar to that of Tc-99m-sulfur colloid. Many investigators believe that In-111 is essentially an reticuloendothelial cell agent.

Tc-99m HMPAO-white blood cells appears to be a good bone marrow imaging tracer. Because granulocytes are normally disposed of in the marrow, the images presumably represent the distribution of marrow reticuloendothelial cells. Although there is considerable liver activity, it is significantly less than the colloid agents, so that the spine is not usually obscured. Labor-intensive labeling procedure makes this technique unpopular. Immunoscintigraphy of the bone marrow has been carried out with Tc-99m labeled murine monoclonal antibody (Tc-99m-NSAb) directed against nonspecific cross-reacting antigen-95, expressed in the cytoplasm and at the cell membrane of granulocytes in the blood as well as in mature granulopoietic cells in the bone marrow. Granulopoietic bone marrow cells are in 50 to 100 : 1 excess compared with granulocytes in the peripheral blood. Therefore Tc-99m-NSAb distribute primarily to granulopoietic bone marrow following IV injection providing high quality images. However, increasing hepatic and splenic uptake has been reported after repeated injections of murine monoclonal antibody.

Evaluation:

Bone marrow scans are evaluated for the presence or absence of activity in the central marrow, for peripheral extension, and for any focal defects for comparison with white blood cell scans. When erythropoiesis is stimulated, the first response is hypertrophy of the erythroid marrow at the expense of fat in the marrow cavity. This occurs in areas of skeleton that normally contain active marrow. Since the distribution of marrow is normal, scintigraphy cannot detect these early changes. When further expansion of marrow tissue is needed, the marrow space moves peripherally into the long bones and can even involve the small bones of the hands and feet. The expansion is usually centrifugal and symmetrical, but occasionally occurs in an asymmetrical and irregular manner that can cause a patchy appearance on the bone marrow scintigraphy. In reticuloendothelial cells scans, the liver and spleen are evaluated for size and presence of any defects, while in radioiron scans, evidence of significant splenic uptake would indicate extramedullary hematopoiesis.

Comparison with other Techniques:

The other techniques available for the evaluation of bone marrow are bone marrow aspiration biopsy and MRI. Bone marrow biopsy is an excellent techniques for evaluating bone marrow and provides a specific clinical diagnosis. Since biopsy is limited to a small part of the total blood-forming organ, it is prone for sampling errors. Radionuclide bone marrow imaging is a simple noninvasive technique that provides information about the whole body distribution of functioning bone marrow in various clinical states (hematological, malignant and post chemotherapy & radiotherapy) and also aids in the differential diagnosis of osteomyelitis (infection versus normal marrow). Magnetic resonance imaging is a highly sensitive technique for imaging of normal and abnormal marrow and can predict differences between fatty, cellular, fibrotic, and hemosiderotic marrow. However bone marrow scintigraphy is preferred when whole body screening is desired, since the cost of MRI limits its use for this purpose.

References

1. Silberstein B: Nuclear Hematology: The Erythron. In: Nucl Med Annual. 198: Pp 163-174.

2. Datz F, Tayler A: The clinical use of radionuclide bone marrow imaging. Semin Nucl Med, Vol XV, No 3 (July), 1985: 239-257.

3. Kim C, Reske S.N, Abass Alavi: Bone marrow scintigraphy. In: Nuclear Medicine. Robert Henkin, et al (eds) 1996 by Mosby-Year book. Pp 1223-124.

4. Nuclear Medicine Diagnosis and therapy. Herbert CJ, et al (eds) 1996 by Thieme medical Publishers, Inc. New York, NY. Pp 780-784.

Click here to go to Joint Program in Nuclear Medicine home page and Copyright notice. 

J. Anthony Parker, MD PhD, Tony_Parker@bidmc.harvard.edu