Colloid scintigraphy showing red bone marrow extension in patients with prostatic carcinoma.

In 25 of 30 patients with bone metastases from prostatic carcinoma, red bone marrow extension was observed by scintigraphy of the reticuloendothelial system (RES). The degree of bone marrow extension in the lower extremities increased with increasing number of bone metastases. In 8 patients, 15 peripheral metastases were detected, all located in areas with extended red bone marrow. The distal level of bone marrow extension coincided with that of the most distal metastases. This is of importance for the detection of peripheral metastases at risk for fracture. Bone marrow extension was also seen in 5 of 8 patients with prostatic carcinoma without bone metastases and was interpreted as a paramalignant activation of RES.     

Bone marrow scintigraphy in Paget's disease of bone

Sixteen patients with 20 lesions of Paget's disease of bone were studied with bone marrow scintigraphy (colloid), bone tissue scintigraphy and radiography. Bone marrow scintigraphy showed normal or increased colloid uptake in 15 of 20 pagetic lesions, and decreased uptake in 4. Bone tissue scintigraphy showed increased metabolic activity in all lesions and was useful in detecting polyostotic disease as well as the extent of the lesions. Conventional radiography most often showed the typical appearance of Paget's disease, but the changes observed were sometimes difficult to differentiate from malignant disease. However, a preserved or increased reticuloendothelial function in the pagetic lesion contradicts metastatic disease as a differential diagnosis. Bone marrow scintigraphy with radiocolloid is a valuable method in the analysis of Paget's disease of bone.     

Symmetric visualization of the femoral heads in reticuloendothelial bone marrow scanning in adults

Two hundred and twenty seven consecutive patients of either sex aged 15–84 suffering from various benign and malignant disorders were studied by ^99mTc-HSA-MM reticuloendothelial bone marrow scintigraphy. In all patients, symmetric findings concerning visualization or nonvisualization of the femoral heads could be seen. Femoral heads were clearly visualized in 48%, nonvisualized in 43%, and equivocally visualized in 9%. In patients with clearly visualized femoral heads, the bone marrow showed peripheral extension in 81%, whereas in patients with nonvisualized femoral heads, bone marrow extension was observed in only 42%. There was a correlation between the degree of bone marrow extension and the ability to visualize femoral heads. There was no obvious difference between males and females, nor amongst patients with various diseases or treatments, nor between different age groups. Two hypotheses are suggested to explain the correspondence between presence of bone marrow tissue in the femoral heads and peripheral extension of the bone marrow organ. Nonvisualization of the femoral heads alone is insufficient to establish the diagnosis of avascular necrosis.     

Bone marrow uptake of liposome-entrapped spin label after liver blockade with empty liposomes

Using an ESR spectrometer, we studied the time course of the uptake of the liposome-entrapped spin label 2,2,6,6-tetramethylpiperidine-N-oxyl-4-trimethylammonium in liver, spleen, and bone marrow following reticuloendothelial liver blockade. Our results show that suppression of the phagocytic activity of the liver increases the delivery of liposomes to the spleen and bone marrow without substantially altering uptake by the liver.     

Severity of bone marrow involvement in patients with Gaucher's disease evaluated by scintigraphy with 99mTc-sestamibi.

Gaucher's disease is a lysosomal storage disorder due to a genetically transmitted deficiency of the enzyme glucocerebrosidase. In the most common form of the disease (type 1), accumulation of glucosylceramide in the reticuloendothelial cells of liver, spleen, and bone marrow leads to visceromegaly, anemia, thrombocytopenia, and osteopenia. Skeletal manifestations secondary to infiltration of the bone marrow by Gaucher's cells are detectable by radiography only in advanced stages. Imaging of bone marrow involvement can be performed indirectly by magnetic resonance techniques or by bone marrow scintigraphy with radiocolloids. However, both procedures lack specificity because the normal bone marrow, rather than the pathologic process, is imaged. The aim of this study was to assess the reliability of (99m)Tc-sestamibi scintigraphy for direct evaluation of bone marrow involvement. METHODS: Seventy-two patients with type 1 and 2 patients with type 3 Gaucher's disease (35 males, 39 females) were enrolled in the study. The mean age +/- SD was 31.9 +/- 16.5 y (range, 3-76 y), and the average duration of the disease manifestations when performing scintigraphy was 12.95 y (median, 10.5 y; range, 0-44 y). Forty-three of 74 patients had never received enzyme replacement therapy (ERT), whereas 31 patients were already being treated with ERT. (99m)Tc-Sestamibi was injected intravenously (6-8 MBq/kg of body weight) and imaging was recorded at the lower limbs 30 min after injection, at the plateau of tracer accumulation in the involved bone marrow. The scans were evaluated visually, assigning a semiquantitative score based on the extension and intensity of uptake in the bone marrow of the lower limbs (0 = no uptake; 8 = maximum uptake). The scintigraphic score was entered into complex statistical analysis, which included a series of clinical and blood chemistry parameters defining overall severity of the disease. RESULTS: (99m)Tc-Sestamibi scintigraphy showed that 71 of 74 patients had some degree of bone marrow involvement. The scintigraphic score was highly correlated with an overall clinical severity score index (SSI) and with various parameters contributing to the SSI, either positively or negatively. The highest correlation of the scintigraphic score was found with an overall biochemical marker of disease severity (serum chitotriosidase). ERT-naive patients showed high correlation of the scintigraphic score with the clinical SSI, with a radiographically based score, and with serum chitotriosidase. In the ERT-treated patients, the scintigraphic score was correlated with the clinical SSI, with hepatomegaly, and with hemoglobin. CONCLUSION: (99m)Tc-Sestamibi uptake reliably identifies bone marrow infiltration by Gaucher's cells. The scintigraphic score is helpful for defining the severity of bone marrow involvement and for comparing patients. (99m)Tc-Sestamibi scintigraphy, which provides topographic information about the sites involved by the disease, is highly correlated with other parameters of disease severity and appears to correlate with response to ERT.     

Monitoring radiation-induced changes in bone marrow histopathology with ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI.

The purpose of this study was to monitor radiation-induced alterations of the blood-bone marrow barrier (BMB) and the reticuloendothelial system (RES) with AMI-227-enhanced magnetic resonance imaging (MRI). Twenty New Zealand white rabbits (n = 10 following total body irradiation and n = 10 controls) underwent AMI-227-enhanced MRI. Pulse sequences included dynamic fast low-angle shot (FLASH; TR/TE 50/4 msec, flip angle 60 degrees) MRI and static T1- and T2-weighted spin-echo (SE) and turbo-SE sequences of the lumbar spine and sacrum. Bone marrow enhancement was quantified as delta signal intensity (SI) (%) =|[(SIpost - SIpre)/SIpre] x 100%| and compared with histopathology, including iron stains and electron microscopy. Dynamic bone marrow deltaSI (%) data steadily increased up to 10-15 minutes after AMI-227 administration, while blood deltaSI (%) data stayed nearly constant, histologically corresponding to iron oxide leakage into the bone marrow interstitium. This bone marrow contrast enhancement increased significantly following irradiation, corresponding to alterations of the endothelial lining of the bone marrow sinusoids. Late postcontrast images exhibited a significant positive T1 enhancement and negative T2 enhancement of the normal bone marrow, which further increased with irradiation due to increased RES activity. Irradiation-induced changes in bone marrow physiology could be reliably assessed with AMI-227-enhanced MRI.     

Bone marrow scintigraphy with 99m Tc labelled monoclonal anti-NCA 90 Fab' fragment: a feasibility study and comparison of bone marrow uptake with 99m Tc labelled monoclonal anti-NCA 95 antigranulocyte antibody

The aim of this retrospective study was to evaluate the usefulness of 99mTc labelled monoclonal anti-NCA 90 antigranulocyte antibody Fab' fragment (MN3 Fab') as a bone marrow imaging agent. One hundred and ten planar scans (88 patients) of the lumbar and sacroiliac regions as well as whole-body scans were performed after 1, 5 and 24 h. All the scans were evaluated visually and bone marrow uptake was determined semiquantitatively as count density ratio from sacroiliac-minus-background to background area. Results were compared to 50 age-matched patients with normal bone marrow scans obtained with the intact 99mTc labelled monoclonal anti-NCA 95 antigranulocyte antibody (BW 250/183) in a previous study. Seventy-three patients showed a physiological activity distribution in the central bone marrow. Ten patients showed a bone marrow extension, while in two patients central bone marrow depression was observed. Evaluation of the ribs, lower thoracic and upper lumbar spine was hampered by soft-tissue activity. Bone marrow uptake was 1.36+/-0.56 after 1 h, decreased thereafter and was significantly lower than that of BW 250/183 (P < 0.001). In conclusion, MN3 Fab' cannot be recommended for bone marrow scintigraphy, because relevant parts of the haemopoietically active bone marrow are not accessible to visual evaluation. A significant role of the semiquantitative evaluation of MN3 Fab' bone marrow uptake in patients with potential marrow depression seems unlikely.     

The bone marrow scan in experimental osteomyelitis

Osteomyelitis causes an inflammatory reaction within the bone marrow early in its course, suggesting that bone marrow imaging with Tc-sulfurcolloid could be used for early detection of the disease. To test this hypothesis, 11 rabbits were inoculated with Staphylococcus aureus, 7 adults in the bone marrow and 4 immature rabbits in the epiphyseal plate. Six rabbits developed osteomyelitis by radiographic and pathologic criteria. Each demonstrated a marked decrease in reticuloendothelial function in the area of osteomyelitis, 4–11 days before radiographic changes were noted. The bone marrow scan was normal in septic arthritis, which was present in some animals before osteomyelitis became evident. These findings suggest that the bone marrow scan is a potentially useful study in early detection of osteomyelitis.Supported by grant UFPHF GM 10548 NIH, Bethesda, Md.     

Bone marrow immunoscintigraphy in haematological patients with pancytopenia: preliminary results

The aim of this study was to assess the clinical value of bone marrow immunoscintigraphy using the (99m)Tc labelled anti-NCA-95 antigranulocyte antibodies (AGAb) and of AGAb bone marrow uptake ratio (UR) in the initial diagnostic work-up of diseases with depression of the bone marrow. Twenty-four whole-body bone marrow scans were performed in 23 patients (11 women, 12 men; median age 46 years, range 17-74 years) 5 h after i.v. injection of 370 MBq of AGAb. The UR was calculated from the posterior view drawing an irregular region of interest around the sacroiliac and a background areas. The mean UR in pancytopenic patients was 2.3+/-1.5 (range 0.3-5.8), thus being significantly lower (P=0.45 x 10(-6)) than the mean UR in a control group of 50 patients (mean UR 7.3+/-2.3; range 4.4-12.6) obtained previously. Considering patient age, there was no overlap between UR of pancytopenic patients and the respective normal ranges. The bone marrow appearance on scans seemed to be characteristic for the different haematological diseases investigated. In six patients with myelofibrosis, bone marrow scans demonstrated diffusely decreased bone marrow activity and prominent splenic uptake, possibly related to extramedullary haematopoiesis. In aplastic anaemia, highly reduced and patchy marrow uptake was observed in four patients (five scans), in one of them persisting even after blood cell counts had recovered to the near-normal range. In another two patients with aplastic anaemia, diffusely decreased bone marrow uptake was obtained. In patients with myeloid leukaemia, bone marrow patterns were almost normal probably because the target antigen is often expressed on neoplastic myeloid cells, too. Bone marrow extension was a common finding in these patients. There is an obvious differentiation between haematological patients with pancytopenia and normal subjects by means of AGAb bone marrow uptake ratio. The distinct patterns of AGAb distribution may be indicative for particular haematological diseases.     

Distribution of the extrahepatic uptake in liver diseases as recorded by scintigraphy

Liver scintigraphy performed with 99Tcm-S and Sn colloid ought to be named RES scintigraphy as the distribution of the colloid is mainly determined by the phagocytic capacity of the RES but also by the regional blood flow and the features of the colloid. Both diffuse hepatocellular disease and malignant disease may have decreased activity in the liver and increased extrahepatic activity: spleen, bone marrow and lungs. In liver cirrhosis at least 3 types of distribution of activity can be recognized: (a) equal increase in spleen, bone marrow and lungs, (b) mainly increase in spleen, and (c) mainly increase in bone marrow and lungs. Therefore a ratio between the total extrahepatic and the hepatic activity ought to be calculated rather than a spleen/liver ratio.     

Technetium-99m MDP scintigraphy. An insensitive tool for the detection of bone marrow metastases

Seventy-nine cases with known carcinoma of the lung or breast who underwent both bone marrow aspiration and Tc-99m MDP bone scintigraphy were reviewed. The bone images were assessed for the presence of the pattern of bone marrow expansion which is visualized by diffuse increased metaphyseal activity, particularly evident at the knees, ankles, and elbows. This pattern was found to be an insensitive marker for the presence of marrow metastases (sensitivity 15%). The specificity of the finding was 86%. When diffuse increased metaphyseal activity is present on a Tc-99m MDP bone scan in a patient with malignant disease, the possibility of bone marrow metastases should be pursued by marrow aspiration and biopsy.     

Autosomal recessive osteopetrosis: bone marrow imaging.

Technetium-99m sulfur colloid scintigraphy was performed prospectively in 12 infants and children with autosomal recessive osteopetrosis, to correlate the appearance of bone marrow stores with advancing age. Baseline images were obtained in all patients, and one to five follow-up images were obtained in eight patients after they began therapy with calcitriol, interferon-gamma, or both. Conventional radiography was performed along with the nuclear studies in all cases. Magnetic resonance (MR) images of the head or lower extremities were also obtained in six patients and were correlated with the scintigraphic findings. Patterns of abnormal distribution of bone marrow appeared to be age-dependent. In patients younger than 1 year, marrow stores were primarily in the skull base and at the ends of the long bones. In patients aged 3-5 years, marrow stores shifted to the diaphyseal regions of long bones and to the calvarium. In the appendicular skeleton, areas of greatest bone marrow activity corresponded to regions of relative decreased opacity on radiographs and areas of intermediate or high signal intensity on T2-weighted MR images. The skull base showed appreciable marrow activity in spite of densely sclerotic bone on radiographs.     

Scintigraphy with nanocolloid Tc 99m in patients with small cell lung cancer, with special reference to bone marrow and hepatic metastasis

Nineteen patients with newly diagnosed small cell lung cancer (SCLC) were examined with a nanocolloid Tc-99m bone marrow whole body imaging (scintigraphy) in order to detect bone marrow metastasis. Bilateral bone marrow biopsy taken from the posterior iliac crest was used as a reference. The scintigraphy was considered abnormal if a focal lesion was present and/or if the bone marrow activity expanded to more than one-third of the proximal part of the extremities. In 3 of the 19 patients, microscopical bone marrow metastasis and cold spots (focal lesions) on the scintigram were present. An additional 9 patients had expansion of the activity. Eight patients showed scintigraphic focal lesions in the liver. SCLC metastasis was confirmed in 4 patients, while 1 patient had focal necroses. The results indicate that cold spots rather than expansion of activity with bone marrow scintigraphy detected bone marrow involvement of the disease in patients with SCLC.     

Venoocclusive liver disease after bone marrow transplantation: findings at duplex sonography.

Ascites, thickening of the gallbladder wall, and reversal of portal flow are documented sonographic findings in venoocclusive disease of the liver. The frequency and specificity of these findings and their relationship to the severity of this disease have not been studied. In an attempt to clarify these issues, 65 patients who had bone marrow transplantations were prospectively studied with serial B-scans and duplex color Doppler sonography. For all patients, assessment included liver size and texture, thickening of the gallbladder wall (greater than 10 mm), and presence of ascites. Doppler flow velocity profiles were obtained from the portal vein, hepatic veins, and inferior vena cava. The hepatic artery resistive index (RI) was calculated. Twenty volunteers were also studied to establish normal flow values. Nineteen patients had documented venoocclusive disease, nine had hepatic graft-vs-host disease (GVHD) (five after proved venoocclusive disease), two had hepatitis, and 40 had no clinical or biochemical evidence of liver injury after bone marrow transplantation. Ascites (n = 16), thickening of the gallbladder wall (n = 8), hepatomegaly (n = 8), and altered liver texture (n = 3) were not distinguishing features of venoocclusive disease. Mean hepatic artery RI was as follows (ranges are in parentheses): control group, 0.69 (0.58-0.76); venoocclusive disease patients, 0.81 (0.75-0.87); GVHD patients, 0.69 (0.63-0.71); all other patients after bone marrow transplantation, 0.66 (0.61-0.71). The RI values in venoocclusive disease were significantly elevated, but an incremental rise in RI with increasing severity of the disease was not seen. Abnormalities in portal vein flow were seen in only two patients: in one with fatal venoocclusive disease, reversed portal flow developed, and in one with GVHD, portal vein thrombosis developed. Contrary to previous reports, no correlation between abnormalities in portal flow and venoocclusive disease was seen. Flow velocities in the hepatic veins and the inferior vena cava were not significantly different from values in the volunteer group. These results suggest that a significant elevation of the hepatic artery RI may be a sensitive index of liver damage related to venoocclusive disease after bone marrow transplantation and an important distinguishing sonographic feature.     

MR imaging of bone marrow in glycogen storage disease type IB in children and young adults.

OBJECTIVE: Patients with glycogen storage disease type IB have neutropenia and neutrophil dysfunction that predispose them to frequent infections, for which they are given granulocyte colony--stimulating factor. Because neutropenia is a consequence of defects in myeloid maturation, the bone marrow aspirations show hypercellularity due to myeloid hyperplasia. This study evaluated MR imaging of bone marrow in glycogen storage disease type IB with and without granulocyte colony-stimulating factor. CONCLUSION: As confirmed by the histologic results in bone marrow aspirations, abnormal findings on MR images of bone marrow in patients with glycogen storage disease type IB indicate an increased myelopoietic activity, which is augmented by treatment with granulocyte colony-stimulating factor.     

Radiopharmaceuticals for spleen and bone marrow studies

The spleen and bone marrow have important hematologic functions. Evaluation of bone marrow alone may be incomplete, unless the function of the spleen is studied also. In addition to hematologic functions, each organ has unique characteristics that may need to be evaluated in assessing its activity. The evaluation of the distribution of reticuloendothelial cells, through the phagocytosis of radioactive particles, provides the basis for most of the morphological and functional studies of these organs. During the past three decades, a variety of radioactive agents have been prepared and examined. Among them, colloids of 99mTc, heat-damaged 99mTc labeled RBCs, and the radionuclides of iron and indium, make possible the functional and morphological examination of the spleen and bone marrow by external scintigraphy.     

Tc-99m HMPAO-labeled leukocytes for hematopoietic marrow imaging. Comparison with In-111 chloride.

The current study was initiated to define whether Tc-99m leukocyte imaging, compared to In-111 chloride imaging, could provide additional information on the hematopoietic activity of the bone marrow in diffuse hematologic disorders. A total of 11 patients with hematologic disorders were studied both with Tc-99m leukocytes and In-111 chloride. One patient with myelofibrosis showed disparate tracer distribution in the bone marrow between the two; Tc-99m leukocyte uptake in the central marrow was highly decreased, whereas In-111 chloride showed expanded marrow. The disparate results of granuloid hypoplasia and erythroid hyperplasia obtained by bone marrow biopsy and aspiration in this patient were thought to give an explanation for the radionuclide findings. The remaining 10 patients showed similar tracer distribution in the marrow, and the observation of hematopoietic cellularity confirmed by bone marrow biopsy and aspiration correlated well with the radionuclide findings. These results demonstrate that Tc-99m leukocytes may be a potential imaging agent for evaluating hematopoietic activity in the bone marrow, in particular granulopoietic activity.     

Increased bone marrow uptake on Tc-99m DMSA scintigraphy in a patient with renal osteodystrophy

A 16-year-old male patient was evaluated with Tc-99m Diethylenetriamine-pentaacetic acid (DTPA) and Tc-99m 2–3 Dimercaptosuccinic acid (DMSA) scintigraphy for renal failure secondary to renal calculi. The uptake in the renal cortex was significantly decreased both on DMSA and DTPA studies. Uptake calculation on DMSA scintigraphy in the kidneys disclosed values of less than 5 %. The activity in the liver and bone was significantly increased. A bone scan performed with Tc-99m methylene diphosphonate (MDP) revealed increased bone uptake with decreased soft tissue activity. Findings on bone scan were compatible with super scan, most likely due to renal osteodystrophy. This case illustrates the altered biodistribution of Tc-99m DMSA and a shift of the radiopharmaceutical to the bone marrow which is mot likely related to colloid formation due to changes in mineral balance in patients with renal failure.     

Radionuclide imaging of bone marrow disorders

Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as ^99mTc-nanocolloid, ^99mTc-sulphur colloid, ¹¹¹In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using ¹⁸F-FDG and ¹⁸F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed.     

The uptake of 111In in the liver and bone marrow of partially hepatectomized and venesectioned rats.

Indium-111 ((111)In) has a strong binding affinity for transferrin (Tf), and the (111)In-Tf complex binds to Tf receptor in various tissues. In partial hepatectomy (PH), a part of blood in circulation is lost along with removed liver tissues; consequently, the number of blood cells and the amount of Tf in circulation decreases. These decreases should greatly affect the uptake of (111)In in the liver and bone marrow. In order to investigate this effect, we compared the uptake in partially hepatectomized rats with that in venesectioned rats, in which only the volume of blood in circulation had been decreased. Our data show that fewer blood cells and smaller amount of Tf in circulation due to venesection increased the uptake of (111)In in bone marrow, but not in the liver, whereas PH increased the uptake of (111)In in both bone marrow and liver. The higher bone marrow uptake of (111)In must be related to the increase of the hematopoietic function resulted from the smaller amount of blood; the higher uptake in liver may be closely related to liver regeneration.