Evaluation of bone marrow cellularity by magnetic resonance imaging in patients with myelodysplastic syndrome Depaoli L, Davini 0, Foggetti MD, Ficara F, Priotto C, Cirillo R, Resegotti L. Evaluation of bone marrow cellularity by magnetic resonance imaging in patients with myelodysplastic syndrome. Eur J Haematol 1992: 49: 105-107.
Abstract: Magnetic resonance imaging (MRI) is a safe modality for examining the bone marrow and it is quite effective in revealing marrow involvement in hematological malignancies. MRI has been compared with needle marrow biopsy in 22 patients with myelodysplastic disorders. A fairly good concordance has been demonstrated in 79% of cases. However, in 5 patients MRI revealed that bone marrow hyperplasia was not generalized. Therefore in elderly patients with MDS, MRI of the spine allows the quantification of bone marrow hyperplasia with a greater accuracy than bone marrow biopsy and this may be useful for monitoring the effect of cytostatic treatment.
Introduction
Several neoplasms may develop into the bone marrow either because they arise from hemopoietic cells or by being introduced through the vascular network of the marrow (metastases). The preferred location of these neoplasms is the red marrow; therefore, the changes produced by the tumor are found mostly in the spine, ribs, pelvis and skull. The neoplastic proliferation of myeloid precursors is usually revealed by changes in peripheral blood. However, no relationship exists between the degree of proliferation and the changes in peripheral blood picture. This is especially true for myelodysplastic syndromes in which peripheral blood (PB) cytopenias are the most frequent presenting features in face of a packed bone marrow. Therefore, marrow aspiration and needle biopsy are mandatory in all hematological malignancies for diagnosis and follow-up. However, the information provided by these manoeuvers is qualitative and not quantitative, as it reflects the changes of the whole hemopoietic tissue but does not assess the total marrow mass. Moreover, marrow involvement with solid tumors like Hodgkin’s disease and other lymphomas, but also with some leukemias, for example chronic myeloid leukemia (l), is frequently patchy; thus more than one needle biopsy is recommended for increasing the accuracy of the result. In young adults, the hemopoietic marrow is found
L. Depaoli, 0. Davini *, M.D. Foggetti *, F. Ficara, C. Priotto, R. Cirillo and L. Resegotti @
Department of Haematology and * Institute of Radiology, San Giovanni Battista Hospital, Molinette, Torino, Italy
Key words: rnyelodysplasia - magnetic resonance imaging - bone marrow - marrow/fat ratio Correspondence: Prof. Luigi Resegotti, Dept. Haematology, Ospedale Molinette, Corso Bramante 90, 10126 Torino, Italy Accepted for publication 27 May 1992
in the vertebrae, ribs, skull, and proximal epiphyses of the femur and humeri. As age progresses, a convertion of red to yellow marrow takes place in the lumbar and cervical vertebrae (2), whereas the fatty replacement is much slower in skull and pelvis. Therefore, a single biopsy sample of marrow tissue from the posterior iliac crest is not adequate for assessing the size of the marrow mass. MRI is able to indicate the type of marrow because the lipid protons of yellow marrow have a higher signal intensity than the water protons of red marrow. Thus, MRI may be an effective tool for evaluating the expansion of hemopoietic mass in myelodysplastic syndromes. We undertook MRI in MDS patients to look for the degree of hyperplasia of bone marrow and we compared MRI with needle marrow biopsy. Material and methods
This study was carried out on 22 patients who met all the diagnostic criteria for MDS according to the FAB cooperative group. Eleven had refractory anemia (RA), 1 refractory anemia with ringed sideroblasts (RARS), 9 refractory anemia with excess of blasts (RAEB) and 1 refractory anemia with excess of blasts in transformation (RAEB-t). The characteristics of these patients are shown in Table 1. Bone marrow samples were obtained by needle biopsy for histological studies and by aspiration for standard morphology, cytochemistry, cyto105
Depaoli et al. Table 2. MRI data in comparison with bone marrow histology. Ratio values below 18.0 define a hypercellular marrow. Full agreement between biopsy and MRI is seen in 17 cases
Table 1. Characteristics of the patients
No. patients age
WBC
median range median range
8M cellularity median Erythroblats
range median range
22 65 yr 25-89 3 100/cmm 1000-6500 80% 30- 100 30% 13-77
Male/female Hb median range median ‘Its range median Blasts range
1517 94 gil 61-126 76 000/cmm 13000-231000 3% 0-23
genetics and in vitvo bone marrow cell cultures. The cellularity of bone marrow was evaluated on histological slides, whereas the percentage of blasts and that of erythroblasts was assessed on aspirate marrow films. MRI was carried out using a 0.5 Tesla superconductive scanner (Esatom MR-5000, Esaote Biomedica, Genova, Italy) with surface coils adapted for studying the spine. T 1-weighted spin-echo sequences were performed in each patient at the levels of the cervico-dorsal and dorso-lumbar spine. Contiguous 5-mm thick sagittal slices were selected, employing two excitations. The measurement of the spin-lactice T I relaxation time is a complex, somewhat imprecise and timeconsuming procedure. Therefore, we chose to evaluate the T1 marrow/fat ratio calculated as the ratio between the signal intensity of the bone marrow of the spine and that of the subcutaneous fatty tissue at the corresponding anatomical level. The reliability of this method has been shown by Glazer et al. (3), Ebner et al. (4) and Negendank et al. (5). The signal intensity was measured on the vertebral bodies of C2, C5, D3, D8, L2 and L5 and on the subcutaneous fatty tissue of the corresponding segments and the mean ratio was calculated. These figures were compared with those obtained in patients without hematological disorders. A ratio below 18 defines a hypercellular marrow whereas a ratio above 20.1 is found in normocellular marrow. Values between 18.1 and 20 are considered borderline. Results
The results of MRI in comparison with those of bone marrow biopsy are shown in Table 2. The T1 signal intensity is higher in normal bone marrow (Fig. 1) and lower in hypercellular marrow (Fig. 2), but more reliable information is provided by the T1 marrow/fat ratio. Low values were found in 13 patients, borderline in 3 and normal in 6. When the MRI data are compared with the marrow cellularity measured on bone marrow biopsy specimens, full agreement was found in 17 cases, whereas in the remaining 5 cases bone marrow bi-
106
MRl
Bone marrow biopsy Patient No.
Gender
Age
Cellularity
Blasts
f
64 30 74 68 67 79 67 78 64 63 63 61 70 40 77 89 67 65 75 25 53 63
90% 90% 80% 80% 70% 70% 70% 90% 80% 80% 80% 50% 80% 40% 80% 90% 80% 30% 50% 80% 100% 90%
0% 23%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
f
f m m f m m m f rn m m m m m
f rn rn rn rn
f
5% 7% 7% 0% 1% 13% 0% 0% 10% 0% 1% 1% 5% 6%
0% 0% 4% 3% 6% 5%
Signal intensity
Marrow/fat ratio
24.3 15.3 21.5 16.0 32.0 29.5 27.6 20.0 34.0 8.9 17.3 30.0 27.6 33.5 29.0 26.8 8.5 33.3 32.8 32.8 22.6 22.5
16.1 10.0 10.8 10.0 21.8 17.9 16.7 11.0 22.4 4.8 10.8 19.4 15.5 23.6 18.7 21.3 5.3 21.6 21.7 19.6 12.1 15.2
opsy revealed a hyperplastic marrow in face of normal or borderline TI marrow/fat ratio. No relationship was found between MRI and number of marrow blasts, erythroblasts and degree of peripheral blood cytopenia. Discussion
Myelodysplastic syndromes are disorders of old age when the fatty component of the bone marrow is prominent. The water content of fatty marrow is lower than that of red marrow; therefore, in older people, the MRI characteristics of bone marrow approximate those of fat, i.e., a short T1 and a relatively long T2. The bone marrow hyperplasia which is a typical feature of MDS results in a change of the MRI signal that can be easily detected and quantified. MRI has been successfully used for detecting malignant infiltration of the bone marrow in metastatic cancer (6, 7), in lymphomas (8) and in multiple myeloma, in which MRI proved superior to any other method for detecting bone marrow lesions (lo). Thompson et al. (1 1) and Silingardi et al. (12) investigated NMR in hairy-cell leukemia both at diagnosis and after interferon treatment and found a good correlation between histologic pattern and MRI. In MDS, bone inarrow biopsy reveals hyperplastic marrow in most cases. However, biopsy can offer only a partial picture of the whole tissue. MRI offer
Magnetic resonance imaging in MDS the possibility of assessing the degree of hyperplasia in a very large area. In our series of patients a full concordance between bone marrow biopsy and MRI has been found in 17 of 22 patients. In no case did MRI suggest an increased marrow mass in face of a cellularly normal marrow biopsy. On the contrary, a normal MRI was found in 5 cases in which marrow hyperplasia was suggested by bone marrow needle biopsy. Nuclear magnetic resonance is an expensive procedure and this precludes its widespread use in MDS. However, it may be useful in a few selected patients in whom the assessment of the marrow mass is mandatory in view of a planned aggressive treatment, as well as in some older subjects receiving low-dose ARA-C in whom serial repetition of bone marrow for monitoring the effects of therapy is hardly feasible. Moreover, as recently reported by Negendank et al. (13), MRI can detect abnormalities suggestive of MDS in patients who would otherwise be diagnosed as having aplastic anemia on the grounds of marrow biopsies. Acknowledgments This work was supported by Regione Piemonte - Progetto ricerca finalizzata 147/89. C.P. is supported by a fellowship of Regione Piemonte. L.D. is supported by a fellowship of Comitato Piemontese “Gigi Ghirotti”.
References 1. PORTERBA, SHIEDSAF, OLSOND. Magnetic resonance imaging of bone marrow disorders. Radiol Clin North Am 1986: 24: 269-289.
2. KRICUNME. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol 1985: 14: 10-19. 3. GLAZER HS, LEEJKT, LEVITTRG, et al. Radiation fibrosis differentiation from recurrent tumor by MR imaging. Radiology 1985: 156: 721-726. 4. EBNERF, KRESSELHY, MINTZMC, et al. Tumor recurrence versus fibrosis in the female pelvis: differentiation with MR imaging at 1.5 Tesla. Radiology 1988: 166: 333-340. WG, AL-KATIBAM, KARANES C, SMITH 5. NEGENDANK MR. Lymphomas: MR imaging contrast characteristics with clinical-pathologic correlations. Radiology 1990: 177: 209216. 6. DAMADIAN R. Tumor detection by Nuclear Magnetic Resonance. Science 1971: 171: 1151-1153. 7. DAMADIAN R. ZANERK, HOR D, DI MAIOT. Human tumors detected by Nuclear Magnetic Resonance. Proc Natl Acad Sci 1974: 71: 1471-1473. 8. SHIELDSAF, PORTERBA, CHURCHELEY S, OLSONDO, APPELBOUM FR, THOMASED. The detection of bone marrow involvement by lymphoma using magnetic resonance imaging. J Clin Oncol 1987: 5: 225-230. 9. OLSOND, SHIELDSAF, SCHURICH CJ, PORTERA, Moss AA. Magnetic Resonance Imaging of the bone marrow in patients with leukemia, aplastic anemia and lymphoma. Invest Radiol 1986: 21: 540-546. 10. DAFFNER RH. LUPETIN AR, DASHN, DEEBZL, SEFCZEC RJ, SHAPIRORL. M.R.I. in the detection of malignant infiltration of bone marrow. Am J Radiol 1986: 146: 353-358. JA, SHIELDS AF, PORTERBA, et al. Magnetic 11. THOMPSON resonance imaging of bone marrow in hairy cell leukemia: correlation with clinical response to alpha-interferon. Leukemia 1987: 1: 315-316. 12. SILINGARDI V, DAVOLIO-MARANI S, FREDERICO M, et al. Bone marrow infiltration in Hairy Cell Leukemia after Interferon therapy detected by Magnetic Resonance Imaging. Eur J Cancer Clin Oncol 1989: 25: 209-213. 13. NEGENDANK W. WEISSMAN D, BEY TM, et al. Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders. Blood 1991: 78: 28722879.
107
Abstract: Magnetic resonance imaging (MRI) is a safe modality for examining the bone marrow and it is quite effective in revealing marrow involvement in hematological malignancies. MRI has been compared with needle marrow biopsy in 22 patients with myelodysplastic disorders. A fairly good concordance has been demonstrated in 79% of cases. However, in 5 patients MRI revealed that bone marrow hyperplasia was not generalized. Therefore in elderly patients with MDS, MRI of the spine allows the quantification of bone marrow hyperplasia with a greater accuracy than bone marrow biopsy and this may be useful for monitoring the effect of cytostatic treatment.
Introduction
Several neoplasms may develop into the bone marrow either because they arise from hemopoietic cells or by being introduced through the vascular network of the marrow (metastases). The preferred location of these neoplasms is the red marrow; therefore, the changes produced by the tumor are found mostly in the spine, ribs, pelvis and skull. The neoplastic proliferation of myeloid precursors is usually revealed by changes in peripheral blood. However, no relationship exists between the degree of proliferation and the changes in peripheral blood picture. This is especially true for myelodysplastic syndromes in which peripheral blood (PB) cytopenias are the most frequent presenting features in face of a packed bone marrow. Therefore, marrow aspiration and needle biopsy are mandatory in all hematological malignancies for diagnosis and follow-up. However, the information provided by these manoeuvers is qualitative and not quantitative, as it reflects the changes of the whole hemopoietic tissue but does not assess the total marrow mass. Moreover, marrow involvement with solid tumors like Hodgkin’s disease and other lymphomas, but also with some leukemias, for example chronic myeloid leukemia (l), is frequently patchy; thus more than one needle biopsy is recommended for increasing the accuracy of the result. In young adults, the hemopoietic marrow is found
L. Depaoli, 0. Davini *, M.D. Foggetti *, F. Ficara, C. Priotto, R. Cirillo and L. Resegotti @
Department of Haematology and * Institute of Radiology, San Giovanni Battista Hospital, Molinette, Torino, Italy
Key words: rnyelodysplasia - magnetic resonance imaging - bone marrow - marrow/fat ratio Correspondence: Prof. Luigi Resegotti, Dept. Haematology, Ospedale Molinette, Corso Bramante 90, 10126 Torino, Italy Accepted for publication 27 May 1992
in the vertebrae, ribs, skull, and proximal epiphyses of the femur and humeri. As age progresses, a convertion of red to yellow marrow takes place in the lumbar and cervical vertebrae (2), whereas the fatty replacement is much slower in skull and pelvis. Therefore, a single biopsy sample of marrow tissue from the posterior iliac crest is not adequate for assessing the size of the marrow mass. MRI is able to indicate the type of marrow because the lipid protons of yellow marrow have a higher signal intensity than the water protons of red marrow. Thus, MRI may be an effective tool for evaluating the expansion of hemopoietic mass in myelodysplastic syndromes. We undertook MRI in MDS patients to look for the degree of hyperplasia of bone marrow and we compared MRI with needle marrow biopsy. Material and methods
This study was carried out on 22 patients who met all the diagnostic criteria for MDS according to the FAB cooperative group. Eleven had refractory anemia (RA), 1 refractory anemia with ringed sideroblasts (RARS), 9 refractory anemia with excess of blasts (RAEB) and 1 refractory anemia with excess of blasts in transformation (RAEB-t). The characteristics of these patients are shown in Table 1. Bone marrow samples were obtained by needle biopsy for histological studies and by aspiration for standard morphology, cytochemistry, cyto105
Depaoli et al. Table 2. MRI data in comparison with bone marrow histology. Ratio values below 18.0 define a hypercellular marrow. Full agreement between biopsy and MRI is seen in 17 cases
Table 1. Characteristics of the patients
No. patients age
WBC
median range median range
8M cellularity median Erythroblats
range median range
22 65 yr 25-89 3 100/cmm 1000-6500 80% 30- 100 30% 13-77
Male/female Hb median range median ‘Its range median Blasts range
1517 94 gil 61-126 76 000/cmm 13000-231000 3% 0-23
genetics and in vitvo bone marrow cell cultures. The cellularity of bone marrow was evaluated on histological slides, whereas the percentage of blasts and that of erythroblasts was assessed on aspirate marrow films. MRI was carried out using a 0.5 Tesla superconductive scanner (Esatom MR-5000, Esaote Biomedica, Genova, Italy) with surface coils adapted for studying the spine. T 1-weighted spin-echo sequences were performed in each patient at the levels of the cervico-dorsal and dorso-lumbar spine. Contiguous 5-mm thick sagittal slices were selected, employing two excitations. The measurement of the spin-lactice T I relaxation time is a complex, somewhat imprecise and timeconsuming procedure. Therefore, we chose to evaluate the T1 marrow/fat ratio calculated as the ratio between the signal intensity of the bone marrow of the spine and that of the subcutaneous fatty tissue at the corresponding anatomical level. The reliability of this method has been shown by Glazer et al. (3), Ebner et al. (4) and Negendank et al. (5). The signal intensity was measured on the vertebral bodies of C2, C5, D3, D8, L2 and L5 and on the subcutaneous fatty tissue of the corresponding segments and the mean ratio was calculated. These figures were compared with those obtained in patients without hematological disorders. A ratio below 18 defines a hypercellular marrow whereas a ratio above 20.1 is found in normocellular marrow. Values between 18.1 and 20 are considered borderline. Results
The results of MRI in comparison with those of bone marrow biopsy are shown in Table 2. The T1 signal intensity is higher in normal bone marrow (Fig. 1) and lower in hypercellular marrow (Fig. 2), but more reliable information is provided by the T1 marrow/fat ratio. Low values were found in 13 patients, borderline in 3 and normal in 6. When the MRI data are compared with the marrow cellularity measured on bone marrow biopsy specimens, full agreement was found in 17 cases, whereas in the remaining 5 cases bone marrow bi-
106
MRl
Bone marrow biopsy Patient No.
Gender
Age
Cellularity
Blasts
f
64 30 74 68 67 79 67 78 64 63 63 61 70 40 77 89 67 65 75 25 53 63
90% 90% 80% 80% 70% 70% 70% 90% 80% 80% 80% 50% 80% 40% 80% 90% 80% 30% 50% 80% 100% 90%
0% 23%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
f
f m m f m m m f rn m m m m m
f rn rn rn rn
f
5% 7% 7% 0% 1% 13% 0% 0% 10% 0% 1% 1% 5% 6%
0% 0% 4% 3% 6% 5%
Signal intensity
Marrow/fat ratio
24.3 15.3 21.5 16.0 32.0 29.5 27.6 20.0 34.0 8.9 17.3 30.0 27.6 33.5 29.0 26.8 8.5 33.3 32.8 32.8 22.6 22.5
16.1 10.0 10.8 10.0 21.8 17.9 16.7 11.0 22.4 4.8 10.8 19.4 15.5 23.6 18.7 21.3 5.3 21.6 21.7 19.6 12.1 15.2
opsy revealed a hyperplastic marrow in face of normal or borderline TI marrow/fat ratio. No relationship was found between MRI and number of marrow blasts, erythroblasts and degree of peripheral blood cytopenia. Discussion
Myelodysplastic syndromes are disorders of old age when the fatty component of the bone marrow is prominent. The water content of fatty marrow is lower than that of red marrow; therefore, in older people, the MRI characteristics of bone marrow approximate those of fat, i.e., a short T1 and a relatively long T2. The bone marrow hyperplasia which is a typical feature of MDS results in a change of the MRI signal that can be easily detected and quantified. MRI has been successfully used for detecting malignant infiltration of the bone marrow in metastatic cancer (6, 7), in lymphomas (8) and in multiple myeloma, in which MRI proved superior to any other method for detecting bone marrow lesions (lo). Thompson et al. (1 1) and Silingardi et al. (12) investigated NMR in hairy-cell leukemia both at diagnosis and after interferon treatment and found a good correlation between histologic pattern and MRI. In MDS, bone inarrow biopsy reveals hyperplastic marrow in most cases. However, biopsy can offer only a partial picture of the whole tissue. MRI offer
Magnetic resonance imaging in MDS the possibility of assessing the degree of hyperplasia in a very large area. In our series of patients a full concordance between bone marrow biopsy and MRI has been found in 17 of 22 patients. In no case did MRI suggest an increased marrow mass in face of a cellularly normal marrow biopsy. On the contrary, a normal MRI was found in 5 cases in which marrow hyperplasia was suggested by bone marrow needle biopsy. Nuclear magnetic resonance is an expensive procedure and this precludes its widespread use in MDS. However, it may be useful in a few selected patients in whom the assessment of the marrow mass is mandatory in view of a planned aggressive treatment, as well as in some older subjects receiving low-dose ARA-C in whom serial repetition of bone marrow for monitoring the effects of therapy is hardly feasible. Moreover, as recently reported by Negendank et al. (13), MRI can detect abnormalities suggestive of MDS in patients who would otherwise be diagnosed as having aplastic anemia on the grounds of marrow biopsies. Acknowledgments This work was supported by Regione Piemonte - Progetto ricerca finalizzata 147/89. C.P. is supported by a fellowship of Regione Piemonte. L.D. is supported by a fellowship of Comitato Piemontese “Gigi Ghirotti”.
References 1. PORTERBA, SHIEDSAF, OLSOND. Magnetic resonance imaging of bone marrow disorders. Radiol Clin North Am 1986: 24: 269-289.
2. KRICUNME. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol 1985: 14: 10-19. 3. GLAZER HS, LEEJKT, LEVITTRG, et al. Radiation fibrosis differentiation from recurrent tumor by MR imaging. Radiology 1985: 156: 721-726. 4. EBNERF, KRESSELHY, MINTZMC, et al. Tumor recurrence versus fibrosis in the female pelvis: differentiation with MR imaging at 1.5 Tesla. Radiology 1988: 166: 333-340. WG, AL-KATIBAM, KARANES C, SMITH 5. NEGENDANK MR. Lymphomas: MR imaging contrast characteristics with clinical-pathologic correlations. Radiology 1990: 177: 209216. 6. DAMADIAN R. Tumor detection by Nuclear Magnetic Resonance. Science 1971: 171: 1151-1153. 7. DAMADIAN R. ZANERK, HOR D, DI MAIOT. Human tumors detected by Nuclear Magnetic Resonance. Proc Natl Acad Sci 1974: 71: 1471-1473. 8. SHIELDSAF, PORTERBA, CHURCHELEY S, OLSONDO, APPELBOUM FR, THOMASED. The detection of bone marrow involvement by lymphoma using magnetic resonance imaging. J Clin Oncol 1987: 5: 225-230. 9. OLSOND, SHIELDSAF, SCHURICH CJ, PORTERA, Moss AA. Magnetic Resonance Imaging of the bone marrow in patients with leukemia, aplastic anemia and lymphoma. Invest Radiol 1986: 21: 540-546. 10. DAFFNER RH. LUPETIN AR, DASHN, DEEBZL, SEFCZEC RJ, SHAPIRORL. M.R.I. in the detection of malignant infiltration of bone marrow. Am J Radiol 1986: 146: 353-358. JA, SHIELDS AF, PORTERBA, et al. Magnetic 11. THOMPSON resonance imaging of bone marrow in hairy cell leukemia: correlation with clinical response to alpha-interferon. Leukemia 1987: 1: 315-316. 12. SILINGARDI V, DAVOLIO-MARANI S, FREDERICO M, et al. Bone marrow infiltration in Hairy Cell Leukemia after Interferon therapy detected by Magnetic Resonance Imaging. Eur J Cancer Clin Oncol 1989: 25: 209-213. 13. NEGENDANK W. WEISSMAN D, BEY TM, et al. Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders. Blood 1991: 78: 28722879.
107
