In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome. A magnetic resonance imaging study

Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow-up examinations. At the time of diagnosis the T1 relaxation times of the vertebral bone marrow were significantly prolonged compared with normal values. The T1 relaxation times of the vertebral bone marrow in patients with MDS showed significantly lower values compared with patients with acute leukemia and did not differ from patients with polycythemia vera.     

Increased bone marrow blood flow in polycythemia vera

Bone marrow blood flow was measured in polycythemia vera, in compensatory and in relative polycythemia with a ¹³³Xe washout method. In the treated polycythemia vera bone marrow blood flow was significantly increased compared with the age-matched controls. The fraction of blood flow entering the bone and flowing through the hematopoietic marrow was markedly increased in both the untreated and the treated polycythemia vera. Although the number of observations in compensatory and relative polycythemia was small, the results suggest that bone marrow blood flow is not markedly increased in these disease. The results also suggest that in older patients the simple ¹³³Xe method may support the diagnosis of polycythemia vera.     

Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

PURPOSE: To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. METHODS: Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumbar vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. RESULTS: The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean +/- S.D.: 0.87 +/- 0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean +/- S.D.: 0.34 +/- 0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean +/- S.D. 1.35 +/- 0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean +/- S.D.: 3.50 +/- 2.51%/min vs. 7.13 +/- 1.74%/min, p<0.01). However, there was no significant difference in the washout rate among patients with MDS, CML, polycythemia vera, and normal volunteers. CONCLUSION: Dynamic contrast-enhanced MR imaging of the water fraction provides additional valuable qualitative information about structural changes of the hematopoietic element.     

Whole-body MR imaging for evaluation of bone marrow cellularity in aplastic anemia

The aim of this study was to investigate the usefulness of whole-body MRI(WB-MRI) in the evaluation of cellularity in bone marrow and the distribution of fatty marrow in aplastic anemia. WB-MRI was performed on five patients with aplastic anemia who ranged in age from 62 to 70 years of age, and on four controls with malignant lymphoma who ranged in age from 59 to 67 years. Coronal images were obtained using a body coil with an FOV of 48 cm x 48 cm, and with both fast short T1 inversion recovery(STIR) and spin-echo T1-weighted(T1-WI) in three regions: (1) head to thorax, (2) abdomen to pelvis, and (3) lower extremities. The findings on WB-MRI were compared with those of histological studies of bone marrow at the sternum and the posterior iliac crest. The results were as follows: (1) there was a correlation between the cellularity of histological studies of bone marrow and signal intensity on WB-MRI; (2) WB-MRI could detect the activity of bone marrow; and (3) in a comparison of signal intensity in aplastic anemia and control subjects, there were differences of signal intensity in the central marrow.     

Bone marrow disorders: characterization with quantitative MR imaging

Thirty patients with various hematologic disorders and 15 healthy control subjects underwent quantitative magnetic resonance (MR) imaging of the lumbar spine with spin-echo techniques. Images of patients with infiltrative bone marrow disorders showed significantly more prolonged T1 times than those of control subjects (P less than .001). It was not possible to distinguish different diffuse infiltrative bone marrow disorders on the basis of T1 values. Aplastic anemia could be distinguished from normality because of significantly shortened T1 (P less than .001). A significant correlation was seen between T1 and bone marrow cellularity (r = .74, P less than .001). T2 was of no value in the characterization of bone marrow disorders. Quantitative MR imaging dose not improve the diagnostic potential of bone marrow imaging in the detection of diffuse marrow infiltrates.     

Prolonged T1 relaxation of the hemopoietic bone marrow in patients with chronic leukemia

Eleven patients with chronic leukemia (7 with chronic lymphocytic leukemia and 4 with chronic myeloid leukemia) were evaluated with magnetic resonance (MR) imaging and T1 relaxation time measurements by use of a 1.5 tesla whole body MR scanner. Bone marrow biopsies were obtained from the posterior iliac crest (within 72 hours of the MR examination) in order to provide data on bone marrow cellularity and differential counts. The patients with chronic leukemia all showed a significant prolongation of the T1 relaxation times compared with the normal range for hemopoietic bone marrow.     

Relationship between bone marrow cellularity and apparent diffusion coefficient

This study was performed to determine if there is a relationship between apparent diffusion coefficient (ADC) and cellularity of bone marrow of the posterior ilium. Four groups of various marrow cellularity underwent diffusion-weighted echo-planar imaging: 1) adults with normal hypocellularity (21 patients); 2) adults with normal normocellularity (13 patients); 3) young children with normal hypercellularity (5 patients); and 4) adults with lymphoma-related hypercellularity (3 patients). In all adults, marrow cellularity was confirmed by uni-or bilateral bone marrow biopsies. In children, the iliac marrow was presumed hypercellular because of their ages. A total of 66 ADC values of bone marrow calculated from diffusion-weighted images with b-values of 30 and 300 seconds/mm(2) was evaluated. Hypercellular marrow (normal and lymphoma-related) showed the highest mean ADC, and hypocellular the lowest ADC. Statistically significant differences were found between three groups of normal marrow: hypocellular, normocellular, and hypercellular. There is a positive correlation between ADC and cellularity of bone marrow. J. Magn. Reson. Imaging 2001;13:757-760.     

Magnetic resonance relaxation times of normal tissue in the course of chemotherapy: a study in patients with bone sarcoma

To study the effect of chemotherapy on normal fat, skeletal muscle, and bone marrow, T1 and T2 relaxation times were measured in 15 patients with bone sarcoma before and after each cycle of preoperative chemotherapy. A section plane containing the tumor and if possible the nonaffected extremity was imaged with combined multiecho spin echo and inversion recovery pulse sequences. T1 and T2 relaxation times were calculated in the normal-appearing tissues. Although some variation was found in the values in the individual patient and between patients, no systematic changes of relaxation times of fat, muscle, or bone marrow occurred in the course of treatment. We conclude that the chemotherapy used in bone sarcoma has no effect on relaxation times of normal fat, muscle, and bone marrow, and that therefore these tissues may serve as a reference for the signal intensity of tumor.     

Adipocyte spatial distributions in bone marrow: implications for skeletal dosimetry models.

Few studies have been conducted to quantify the spatial distributions of adipocytes in the marrow cavities of trabecular bone. Nevertheless, such data are needed for the development of 3-dimensional (3D) voxel skeletal models where marrow cellularity is explicitly considered as a model parameter for dose assessment. In this investigation, bone marrow biopsies of the anterior iliac crest were examined to determine the size distribution of adipocyte cell clusters, the percentage of perimeter coverage of trabecular surfaces, and the presence or absence of adipocyte density gradients in the marrow space, all as a function of the biopsy marrow cellularity (5%-95%). METHODS: Biopsy slides from 42 patients were selected as designated by the hematopathologist as either normocellular or with no evidence of disease. Still-frame video image captures were made of 1-3 regions of interest per biopsy specimen, with subsequent image analysis of adipocyte spatial characteristics performed via a user-written MATLAB routine. RESULTS: A predictable shift was found in cluster size with decreasing marrow cellularity from single adipocytes to clusters of >or=3 cells; the percentage of 2-cell clusters remained relatively constant with changing cellularity. Also, a nonlinear increase in trabeculae perimeter coverage was found with increasing fat tissue fraction at marrow cellularities between 50% and 80%. Finally, it was demonstrated that only in the range of 20%-50% marrow cellularity was a slight gradient in adipocyte concentration indicated with adipocytes localized preferentially toward the trabecular surfaces. CONCLUSION: Electron transport simulations were conducted in 4 different 3D voxel models of trabecular bone for sources localized in the active marrow (TAM), bone volume (TBV), bone endosteum (TBE), and bone surfaces (TBS). Voxel model simulations demonstrated that absorbed fractions to active marrow given by the ICRP 30 model (MIRDOSE2) are exceedingly conservative for both TBV and TBS sources, except in the case of high-energy particles (>500 keV) at high values of marrow cellularity (>70%). Values of both phi(TAM<--TBV) and phi(TAM<--TBS) given by the Eckerman and Stabin model (MIRDOSE3) were shown to be reasonably consistent with 3D voxel model simulations at the reference cellularity of 25%, except in the case of low-energy emitters (<100 keV) on the bone surfaces.     

Repopulation of marrow after transplantation: MR imaging with pathologic correlation

Sixty-seven magnetic resonance (MR) studies of the lumbar spine were performed in 15 patients with bone marrow transplants, and the appearance of marrow regeneration on MR images was correlated with results of bone marrow biopsy and pathologic examination. After transplantation, T1-weighted MR images of vertebral marrow showed a characteristic band pattern consisting of a peripheral zone of intermediate signal intensity and a central zone of bright signal intensity. Reciprocal changes were identified on short inversion time inversion recovery images. At histologic examination the central zone corresponded to fatty marrow; the peripheral zone corresponded to a zone of regenerating hematopoietic cells. Posttransplantation T1 and T2 relaxation times of the entire vertebral marrow were calculated from the spin-echo images; no statistically significant trends in relaxation times were noted. Knowledge of the normal MR pattern of marrow regeneration after transplantation may be useful in screening for residual marrow disease, determining marrow engraftment, and differentiating marrow repopulation with normal versus malignant cells.     

Ferumoxides-enhanced quantitative magnetic resonance imaging of the normal and abnormal bone marrow: preliminary assessment

The purpose of our study was to assess the effects of intravenous administration of ferumoxides on normal and abnormal vertebral bone marrow T1 and T2 relaxation times. Changes in bulk T1 and T2 relaxation times induced by intravenous administration of ferumoxides were determined in the normal vertebral marrow of two healthy subjects and four patients. In the four patients, changes in bulk T1 and T2 values induced by furomoxides injection were also determined in 12 vertebral metastases. Relative to precontrast relaxation time values, bulk T1 and T2 values of normal bone marrow had declined by a mean of 24% and 19%, respectively, in the two subjects and the four patients 45 minutes after ferumoxides administration. Relative to precontrast values, bulk T1 and T2 values of abnormal bone marrow had decreased by a mean of 16% and 2%, respectively. Decreases in bulk T1 and T2 values in normal bone marrow and in bulk T1 values in metastases were statistically significant (P<0.001). Changes in bulk T2 values observed in metastases were not statistically significant. Quantitative MRI demonstrates that ferumoxides infusion induces a decrease in bulk T1 and T2 relaxation times of normal bone marrow. It also suggests a lack of T2 shortening in bone metastases.     

Effect of oxygen inhalation on relaxation times in various tissues

The effect of the oxygen inhalation on relaxation times was evaluated in various tissues, including the myocardium, liver, spleen, skeletal muscle, subcutaneous fat, bone marrow, and arterial blood, with a [¹H]MR system. Statistically significant decrease of T1 relaxation times was observed in the myocardium, spleen, and arterial blood after inhalation of 100% oxygen, whereas no significant change was observed in liver, skeletal muscle, subcutaneous fat, or bone marrow. The T2 relaxation time of these tissues did not differ significantly between before and after inhalation of the oxygen. These results indicate that [¹H]MRI can be used to evaluate changes with oxygen inhalation and that the effect of the oxygen inhalation on T1 relaxation time is different among various tissues.     

Magnetic resonance imaging of the metastatic vertebral tumor

Fourty two patients underwent MR studies for a variety of lesions in the vertebral body. A 0.15-T MR system was employed. Twenty five patients were found to have malignant metastatic lesions (group 1); 16 had non-neoplastic lesions (group 2). The ability to discriminate between group 1 and group 2 with MR imaging was evaluated. All malignant metastatic lesions appeared as low intensity areas on both T1-weighted spin echo image and inversion recovery image, but 44 to 53% of the non-neoplastic lesions appeared as low intensity areas, respectively. The diagnostic ability with signal intensity of the vertebral column was evaluated on various pulse sequences; sensitivity of inversion recovery and T1-weighted spin echo image was 100%, in contrast specificity of these pulse sequences was 47 to 56%, overall accuracy was the highest on T1-weighted spin echo image (86%). The signal intensity of intervertebral disk was also evaluated in both groups. The intervertebral disks adjacent to the all malignant metastatic lesions showed normal intensity on both T1-weighted spin echo image and inversion recovery image, but non-neoplastic lesions showed variable intensities on images with all pulse sequences. The diagnostic ability with the signal intensities of the vertebral column and intervertebral disk was higher than that of the vertebral columns alone. Consequently accuracy was the highest in that case of both intervertebral disk and bone marrow which were imaged on T1-weighted spin echo (93%). We concluded that this diagnostic method was useful in distinguishing malignant metastatic from non-neoplastic lesions.     

Characterization of lymphadenopathy by magnetic resonance relaxation times: preliminary results

The purpose of this study was to evaluate the ability of magnetic resonance (MR) to enable characterization of disease within lymph nodes and differentiation between benign and malignant lymph nodes. Ninety-three patients were examined. Normal and malignant lymph nodes were excised from seven patients, and the T1 and T2 relaxation times were analyzed in vitro using spectroscopy. In 86 patients, T1 and T2 relaxation times of the lymph nodes were determined from MR images. Spectroscopic analysis revealed an increase in the T1 and T2 values of nodes involved by neoplasm compared with uninvolved nodes in an individual case. Comparison of measurements from 28 lymph nodes analyzed in vitro using spectroscopy showed an overlap of the T1 and T2 values between normal and malignant lymph nodes. T2 relaxation times and relative spin density values were greater for acute inflammatory nodes than for nodes involved by granulomatous diseases (tuberculosis and sarcoidosis) or nodes replaced by lymphoma or metastasis. Changes in T1 relaxation values were not specific. The measurements of T1 and T2 relaxation times and relative spin density showed an overlap between nonspecific lymphadenopathy, nodes involved by granulomatous diseases, and malignant nodes. Differentiation between these various nonacute types of enlarged lymph nodes could not be achieved using current MR parameters.     

In vivo relationship between marrow T2* and trabecular bone density determined with a chemical shift-selective asymmetric spin-echo sequence.

Magnetic field inhomogeneities due to differences in susceptibility between trabecular bone and bone marrow result in a reduction in T2*. The authors previously quantified the relationship between the relaxation rate enhancement per unit change in bone density, delta R2*, using dried, excised vertebral bodies immersed in saline. In the present study, they investigated the precision and reproducibility of such measurements in vitro and found that the short-term precision ranges from 2% to 11%, while the long-term precision error, which may be governed by the placement of the region of interest, can vary up to 50%. A chemical shift-selective asymmetric spin-echo sequence was used to assess T2* changes in the saturated fat component of bone marrow in vivo. It was shown that the marrow fat relaxation rate increases as the surrounding trabecular bone density increases and that the delta R2* of the marrow fat component was 0.20 sec-1/mg/cm3. The results also indicate that the distribution of T2* varies with image resolution. Both in vitro and in vivo, characteristics of the relaxation time distribution such as the mean, standard deviation, and skewness decrease as image resolution decreases, the degree of variation depending on the density of the surrounding trabecular network.     

Magnetic resonance imaging of the bone marrow in patients with acute leukemia during and after chemotherapy. Changes in T1 relaxation

Twenty-seven patients with acute leukemia were examined at the time of diagnosis with MR imaging and in vivo T1 relaxation time measurements of the hemopoietic bone marrow. A 1.5 T whole body magnetic resonance scanner was used. Twenty of the patients had follow-up examinations in relation to chemotherapy. Bone marrow biopsies from the posterior iliac crest were obtained within a short time interval of all MR examinations. At the time of diagnosis, T1 relaxation times were increased significantly in all the leukemic patients, compared with 24 age-matched controls. A decrease in T1 relaxation time towards or into the normal range was observed in 10 patients who obtained remission. The T1 relaxation time remained prolonged in 6 patients who failed to obtain remission during chemotherapy. Four patients, who obtained remission with concomitant decrease of T1 values towards or into the normal range, also showed prolongation of T1 relaxation time in relation to leukemic relapse. The results indicate that changes observed in T1 relaxation times of the hemopoietic bone marrow in patients with acute leukemia reflect changes in disease activity, and, that serial measurements of T1 values may provide clinically useful information with the possibility for identification of residual disease in regions inaccessible for biopsy.     

Bone marrow imaging: magnetic resonance studies related to age and sex

Measurements of T1 and T2 relaxation values and spin density of the lumbar vertebral bone marrow were performed in 212 patients, and the results were correlated with the patients' age and sex. T1 and T2 relaxation times for bone marrow in the lumbar vertebral bodies showed a progressive decrease with age for both sexes (except for the T2 relaxation values in female patients). The replacement of hematopoietic marrow by fatty marrow could explain the decrease in T1 and T2. The T1 and T2 values were in the same range for the first two age groups (age 1-10 years and age 21-40 years) and became slightly greater for the older female patients (age 51 years and older) than for the older males. This could be due to the loss of bone and mineral content, which is more rapid and significant for women. These normal T1 and T2 values may provide a baseline for future evaluation of diseases involving the lumbar spine.     

The evaluation of the bone marrow accumulation of Ga-67 citrate

The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate.     

In-vivo measurement of spin lattice relaxation time (T1) of bone marrow in healthy volunteers: the effects of age and sex

Magnetic resonance images of the spine, sternum, femoral heads and upper femoral shafts were obtained from 90 healthy volunteers to determine the normal ranges of spin lattice relaxation time (T1) for different regions of the bone marrow. The influence of age, sex and oral contraceptive usage on bone marrow T1 was assessed. Differences observed between the T1 of the various regions of the bone marrow examined were consistent with the expected distribution of erythropoietic cells and fatty marrow. Bone marrow T1 was found to decrease with age, significantly lower mean T1 values being observed in subjects over 40 years of age than for those in the 20-40 years age group. The mean bone marrow T1 of females in the 20-40 years age group was significantly higher than that for males of comparable age. For subjects over 40 years of age, the difference in bone marrow T1 observed between males and females was not significant. Oral contraceptive usage had no effect on bone marrow T1.     

Malignant lymphoma: bone marrow imaging versus biopsy

In 107 patients with malignant Hodgkin and non-Hodgkin lymphoma, bone marrow was evaluated with scintigraphy, magnetic resonance (MR) imaging, and biopsy to detect bone marrow infiltration. Imaging and biopsy results were classified as normal (class 0), suggestive of reactive changes (class 1), or suspicious for infiltration (class 2). About one-half of biopsy and imaging results agreed completely. In patients with chronic lymphocytic leukemia, false-negative findings were frequent with both imaging techniques. Although a positive biopsy result is usually accepted as proof of bone marrow infiltration, results indicate that negative biopsy findings do not exclude tumor involvement. When suspected infiltration was found with MR imaging or scintigraphy but results were normal or suggestive of reactive changes in the first blind biopsy, repeat blind or guided biopsy helped confirm the imaging results. Autopsy findings in two patients completely confirmed previous results with MR imaging and scintigraphy, although findings at antemortem biopsy were different. Scintigraphy and MR imaging should be included routinely in the staging of malignant lymphoma as an adjunct to blind biopsy in the complete evaluation of bone marrow status.