MRI marrow observations in thalassemia: The effects of the primary disease,transfusional therapy,and chelation

The magnetic resonance bone marrow patterns in thalassemia were evaluated to determine changes produced by transfusion and chelation therapy. Thirteen patients had T1-and T2-weighted images of the spine, pelvis and femurs. Three received no therapy (age range 2.5–3 years). Three were “hypertransfused” (transfused to maintain a hemoglobin greater than 10 g/dl) and not chelated because of age (age range 6 months–8 years). Seven were “hypertransfused” and chelated (age range 12–35 years). Signal characteristics of marrow were compared with those of surrounding muscle and fat. Fatty marrow (isointense with subcutaneous fat) was compared with red marrow (hypointense to fat and slightly hyperintense to muscle). Marrow hypointense to muscle was identified as iron deposition within red marrow. The untreated group demonstrated signal consistent with red marrow throughout the central and peripheral skeleton. Hypertransfused but not chelated patients demonstrated marked iron deposition in the central and peripheral skeleton. Hypertransfused and chelated patients demonstrated iron deposition in the central skeleton and a mixed appearance of marrow in the peripheral skeleton. The MR appearance of marrow in thalassemia is a reflection of the patient's transfusion and chelation therapy. Iron deposition occurs despite chelation therapy in sites of active red marrow. As red marrow retreats centrally with age, so does the pattern of iron deposition. The long-term biological effects of this iron deposition are unknown.     

Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR

Background. Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. Objective. The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. Materials and methods. Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. Results. All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. Conclusion. MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow. Received: 20 June 1997 Accepted: 7 November 1997     

Iron overload following bone marrow transplantation in children: MR findings

Objective. The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. Materials and methods. We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. Results. None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P = 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. Conclusion. Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis. Received: 10 June 1997 Accepted: 10 June 1997     

MR marrow signs of iron overload in transfusion-dependent patients with sickle cell disease

Magnetic resonance (MR) marrow signal in the axial and appendicular skeleton of 13 transfusiondependent and chelated pediatric patients with sickle cell anemia (SSD) was compared with marrow signal in six non-transfusion-dependent patients with SSD. Hepatic, pancreatic, and renal MR signal were also evaluated. Indication for hypertransfusion therapy was primarily prior history of stroke. Transfusion-dependent patients had evidence of iron deposition throughout the imaged marrow and the liver, despite deferoxamine chelation therapy. Non-transfusion-dependent patients did not demonstrate grossly apparent signs of iron overload. Red marrow restoration was present in the spine, pelvis and long bones and, in some patients, within the epiphyses. Marrow edema secondary to vaso-occlusive crises was evident in the metaphyses and diaphyses of long bones in areas of both red and fatty marrow and was best seen using fat-saturated T2-weighted imaging techniques.     

Evaluation of bone marrow metastasis of neuroblastoma and changes after chemotherapy by MRI

To evaluate the usefulness of MRI for diagnosing bone marrow metastasis of neuroblastoma, we compared MRI findings with histological findings. MRI was performed 26 times in 20 patients with neuroblastoma to detect metastasis to the bone marrow of the femur and tibia. Abnormal areas observed by MRI were histologically examined. The lesion visualized by MRI as a low-intensity area on T1-weighted images and as a high-intensity area on T2-weighted images was histologically confirmed to be neuroblastoma in 81% (17/21). The percentage varied according to the treatment state: 89% (8/9) by MRI imaging performed before the initiation of chemotherapy, 67% (6/9) within 3 weeks after cessation of chemotherapy (during chemotherapy), and 100% (3/3) in recurrent cases 1 year or more after chemotherapy. During the follow-up period after chemotherapy, tissue with signal intensities similar to that of bone marrow was observed in a speckled pattern in the intramedullary space on T1- and T2-weighted images. This tissue was histologically demonstrated to be normal bone marrow and was considered to be bone marrow remaining after chemotherapy. In this small series, histological findings supported the results of MRI, confirming the usefulness of MRI for diagnosing bone marrow metastasis of neuroblastoma. However, bone marrow metastasis after chemotherapy was difficult to evaluate by comparing signal intensities alone. © 1993 Wiley-Liss, Inc.     

Chronically Transfused Pediatric Sickle Cell Patients are Protected from Cardiac Iron Overload

Iron overload is a major toxicity of chronic transfusions. Myocardial iron overload is associated with cardiac dysfunction. Cardiac and liver magnetic resonance imaging (MRI) was performed on 14 chronically transfused sickle cell disease (SCD) and non-sickle cell disease (non-SCD) patients seen at Vanderbilt Children's Hospital from 1 January 2000 to 10 March 2010. Retrospective review was conducted to assess cardiac T2*, liver T2*, ventricular dimensions and function, echocardiogram, length of transfusion, hemoglobin, and ferritin measurements. Ten patients had SCD and 4 had non-SCD, including α-thalassemia, β-thalassemia, and Diamond-Blackfan anemia. Cardiac T2* was normal in all SCD patients (mean 39 ± 12 ms), but abnormal in 3 of 4 non-SCD patients (mean 11.8 ± 2.4 ms). Liver T2* was similar between SCD (mean 6.2 ± 1.6 ms) and non-SCD patients (mean 5.9 ± 1.9 ms), and did not correlate with serum ferritin. Comparing SCD and non-SCD patients with similar transfusion duration, SCD patients had normal cardiac T2* and non-SCD patients had abnormal cardiac T2*. No patients had cardiomyopathy, but ventricular dilatation was common among SCD patients. Chronically transfused pediatric SCD patients are relatively spared of myocardial iron overload, which is unlikely to be due to lower total body iron burden in SCD patients than non-SCD patients.     

Nuclear magnetic resonance and iron overload in thalassemia]

We assessed the iron load content in 36 beta-thalassemia patients by NMR correlating the results with serum ferritin levels. 22 of them were affected by beta-thalassemia major on hyper-transfusional regimen (Group A), 4 by beta-thalassemia intermedia (Group B) and 10 by beta-thalassemia major, who had been previously bone marrow transplanted (Group C). In A and C Groups the liver showed the lowest signal intensity on spin echo images (p less than 0.01; p less than 0.06, respectively). A significant correlation between the summation of signals obtained from all the examined organs and serum ferritin levels was observed by evaluating both all the patients globally (r = 0.78; p less than 0.001) and the A and C Group patients. This correlation was confirmed only in the liver both in all the patients (r = 0.77; p less than 0.001) and in A and C Group patients, when the signals obtained from each organ were evaluated.     

Chronically transfused pediatric sickle cell patients are protected from cardiac iron overload

Iron overload is a major toxicity of chronic transfusions. Myocardial iron overload is associated with cardiac dysfunction. Cardiac and liver magnetic resonance imaging (MRI) was performed on 14 chronically transfused sickle cell disease (SCD) and non-sickle cell disease (non-SCD) patients seen at Vanderbilt Children's Hospital from 1 January 2000 to 10 March 2010. Retrospective review was conducted to assess cardiac T2*, liver T2*, ventricular dimensions and function, echocardiogram, length of transfusion, hemoglobin, and ferritin measurements. Ten patients had SCD and 4 had non-SCD, including α-thalassemia, β-thalassemia, and Diamond-Blackfan anemia. Cardiac T2* was normal in all SCD patients (mean 39 ± 12 ms), but abnormal in 3 of 4 non-SCD patients (mean 11.8 ± 2.4 ms). Liver T2* was similar between SCD (mean 6.2 ± 1.6 ms) and non-SCD patients (mean 5.9 ± 1.9 ms), and did not correlate with serum ferritin. Comparing SCD and non-SCD patients with similar transfusion duration, SCD patients had normal cardiac T2* and non-SCD patients had abnormal cardiac T2*. No patients had cardiomyopathy, but ventricular dilatation was common among SCD patients. Chronically transfused pediatric SCD patients are relatively spared of myocardial iron overload, which is unlikely to be due to lower total body iron burden in SCD patients than non-SCD patients.     

MRI “road-map” of normal age-related bone marrow

We retrospectively reviewed 733 cranial and 250 spinal T1-weighted MR images of patients younger than 24 years to evaluate the bone marrow changes. The signal intensity of the bone marrow on short-TR/TE images was compared with that of fat and normal muscles in the contiguous region and graded. The signal intensity of all anatomic segments was as low as that of muscle, or inferior, in all patients younger than 3 months because of hematopoietic tissue and probably greater amounts of trabecular bone. The first anatomic segments of cranial bone to become hyperintense were the zygomatic bone and mandibular symphysis, followed by the presphenoid bone, basisphenoid, basiocciput, calvaria, and the petrous apex. After 3 years of age, most patients demonstrated pneumatization of the sphenoid sinus. We describe the most interesting changes in the developing spien, which occur in the first 2 years of life. The morphology of the vertebral bodies was evaluated. The variability of the signal and the morphology of the disks were also evaluated. Regional patterns of bone marrow signal intensity and age-related differences should not be misinterpreted as a pathologic condition.     

Comparison of turbo inversion recovery magnitude (TIRM) with T2-weighted turbo spin-echo and T1-weighted spin-echo MR imaging in the early diagnosis of acute osteomyelitis in children

Objective. To compare turbo inversion recovery magnitude (TIRM) with standard T1-weighted (T1-W) and T2-weighted (T2-W) MR sequences in the very early detection of acute osteomyelitis in children. Materials and methods. In 15 children with osteomyelitis, 15 sets of T1-W spin-echo (SE) (TR/TE, 400–640/12–17), T2-W turbo spin-echo (TSE) (TR/TE/ETL, 3290–4465/112–120/11), and TIRM (TR/TE/TI, 4000–6120/60/160) images were acquired with a 1.0-T magnet. Contrast-to-noise (C/N) ratios and percentage of signal between lesion and normal bone marrow were analysed with a computer-assisted image analysing system in a region of interest (ROI). Results. In 13 of 15 patients, the absolute signal enhancement in a ROI on the TIRM images was better than on the T1-W SE and T2-W TSE images and in 14 of 15 cases, C/N ratios were also better on the TIRM images than on the other sequences. In the other cases, the TIRM signal was diagnostically equivalent. On the TIRM images, the signal difference between normal and pathological tissue was increased to 43–281 % (mean 124 %). On the T2-W TSE images, this signal difference was 4–79 % (mean 36 %) and on the T1-W SE images 6–77 % (mean 37 %). Conclusion. The TIRM sequence is highly sensitive for detecting bone marrow oedema in the very early stage of acute osteomyelitis in children. MRI utilising the TIRM sequence allowed for an early diagnosis. With scan time of less than 4 minutes, this sequence is superior to T1-W SE and T2-W TSE images for detecting early osteomyelitis-associated bone marrow oedema. Received: 18 August 1997 Accepted: 17 June 1998     

MRI T2*技术对中、重型β地中海贫血患者心脏及肝脏铁沉积状态的评估

目的：了解中、重型β地中海贫血患者体内铁沉积状况。方法：对39例中、重型β地中海贫血患者的输血、排铁的情况进行统计,检测患者体内铁蛋白水平,并运用MRI T2*技术检测心脏及肝脏铁沉积状况。结果：患者血清铁蛋白水平最低为1500 ng/mL,最高达 11491 ng/mL。肝脏铁重度沉积者15例（38%）,中度沉积者15例（38%）,轻度沉积者7例（18%）,正常者 2例（5%）。 心脏铁重度沉积者7例（18%）,轻度沉积者5例（13%）,正常者27例（69%）。1例出现心律紊乱症状,4例年龄超过20岁者均呈现性腺功能发育不全。大多患者因家庭经济原因未能进行规律输血及排铁治疗,且开始排铁时间较晚。患者血清铁蛋白水平与开始排铁的时间、剂量密切相关。结论：未进行早期规律的输血和排铁治疗的地中海贫血患者,体内铁的沉积发生年龄早,易早期出现重要器官的功能损害而引发相关并发症,应引起临床医师和患者家属的高度重视并制定相应的诊疗措施提高患者的生活质量。     

Current concepts in the management of thalassemia

The thalassemias are a group of hereditary disorders in which there is a decreased production of one or more of the normal polypeptide chains of hemoglobin. In recent years with the advent of modern transfusion regimens the complications associated with chronic anemia and compensatory erythroid hyperplasia are rarely seen. The clinician is now faced with treating the complications related to repetitive transfusion therapy, including transfusional hemosiderosis, transmission of viral illnesses and proper timing of splenectomy. Chelation therapy for iron overload is an integral part of therapy and requires strict compliance if maximal benefits are to be achieved. Future areas of research include development of oral iron chelators, bone marrow transplantation and methodology for stimulating fetal hemoglobin production.     

Bone pain in thalassaemia: assessment of DEXA and MRI findings

An increasing number of adult thalassaemics have been complaining of aches and pains of varying degrees of severity. In a minority the pains are debilitating and there is stiffness in movement. This study is an attempt to understand the osteoporosis of thalassaemia using DEXA and MRI as the main investigative tools. 122 patients with homozygous beta-thalassaemia were examined by DEXA. It was found that almost half had BMD below two standard deviations from the mean for the normal population, especially in the lumbar spine. There was no marked worsening with age. However the proportion of patients who had their first transfusion after the 3rd year (especially after the 6th) was significantly greater in those with the low BMD. There is also an excess of hypogonadic thalassaemics amongst those with low BMD. 72 thalassaemics were examined by MRI of marrow. Hypercellular, dark marrow on T1 weighted images found in young patients (20-30 yr) was replaced by fatty marrow in later life (30-40 yr). In a group of 21 older thalassaemics (33-62 yr) extreme bone marrow expansion was expressed by the reappearance of hypercellular areas, giving the impression of patchiness which affects not only the diaphyses but also the metaphyses. These patients mostly (66%) had thalassaemia intermedia and had started irregular transfusion after the 6th year of life. About 75% had a BMD below 2 SD. The conclusion is that patients who were late in receiving blood and especially those with thalassaemia intermedia had a more expanded bone marrow with pressure on cortical bone which caused pain in several cases. An attempt was made in 10 patients to reduce marrow hyperplasia by using hydroxyurea. Results showed a relief of pain and modification of magnetic signal intensity.     

Pigmented villonodular synovitis. Diffuse and localized forms in children]

Pigmented villonodular synovitis (PVS) is characterized by a locally aggressive synovial proliferation that engenders progressive destruction of cartilage and bone. Two cases, a diffuse and a localized form, are reported. CASE REPORT: 1) A 9.9-year-old boy followed up for a popliteal cyst presented with chronic arthritis of the left knee. Aspiration yielded a bloody synovial fluid. MRI showed a heterogeneous synovial process with decreased signal in both T1- and T2-weighted images. The diagnosis of PVS was made on histology of an excisional biopsy. A complete open synovectomy was then performed. 2) A 13.8-year-old boy had a palpable mass on the internal side of the right patellofemoral joint. MRI showed a heterogenous mass with areas of hypointensity on all spin echo sequences corresponding to hemosiderin deposits suggestive of PVS. Surgical excision of a reddish-brown circumscribed lesion was performed. Diagnosis of PVS was made at surgery and confirmed by histologic examination. CONCLUSION: PVS diagnosis is frequently delayed due to nonspecific symptoms. Bloody fluid aspiration and MRI are valuable tools for early diagnosis. Treatment is surgical: extensive synovectomy for the diffuse form, excision of the lesion for the localized form.     

Magnetic resonance imaging of the brain in very preterm infants: visualization of the germinal matrix, early myelination, and cortical folding

OBJECTIVE: To investigate preterm infants, we have installed in our neonatal intensive care unit a dedicated magnetic resonance (MR) imaging system which was specifically designed for neonatal use. The aim of this study was to describe the MR appearances of the brain in preterm infants who were first scanned between 25 and 32 weeks gestational age (GA) and to outline changes to the brains of these infants between their first scan and term. METHODS: Preterm infants of 25 to 32 weeks GA were imaged using the 1T neonatal MR system (Oxford Magnet Technology, Eyensham, Oxfordshire, England/Picker International, Cleveland, OH). The scanning protocol included T1-weighted conventional spin echo (repetition time [TR], 600; echo time, 20 ms), inversion recovery fast spin echo (TR, 3530; effective echo time, 30; inversion time, 950 ms), and T2-weighted fast spin echo (TR, 3500; effective echo time, 208 ms) sequences. RESULTS: Seventeen infants of median 28 weeks GA (range, 24 to 31 weeks) at birth were imaged a total of 53 times between birth and term. The median number of images per infant was two (range, 1 to 9). In infants of < 30 weeks GA, the germinal matrix was visualized at the margins of the lateral ventricles. It had a short T1 and short T2 and the bulk of it involuted at between 30 and 32 weeks GA. The white matter had a relatively homogeneous low signal except for bands of altered signal (probably originating from regions containing radial glia and migrating cells) which were most apparent anterolateral and posterolateral to the lateral ventricles. Myelination was seen in the posterior brainstem, cerebellum, and region of the ventrolateral nuclei of the thalamus. Infants had very little cortical folding at 25 weeks GA but this developed later in an orderly fashion. CONCLUSION: The neonatal MR system allowed extremely preterm infants to be studied safely with MR imaging. The images acquired demonstrated the germinal matrix, early myelination, and early cortical folding. Evolution of these features was demonstrated with serial studies.     

MR signal characteristics of cadaveric bone allografts in three children with primary bone tumors treated with limb salvage therapy

Three children with adult cadaveric bone allografts for the treatment of bone malignancies are presented. Follow-up magnetic resonance (MR) imaging demonstrated decreased signal on T1-weighted imaging and increased signal on T2-weighted imaging in the allograft without clinical evidence of recurrent disease. These signal characteristics appear to be a normal finding in cadaveric bone allografts and should not be mistaken for recurrence. The finding may reflect persistent marrow necrosis within the allograft marrow cavity.     

Prognostic importance of magnetic resonance imaging in bone marrow involvement of Hodgkin disease

BACKGROUND: Determination of bone marrow involvement is important in staging Hodgkin disease (HD), so we compared the effectiveness of magnetic resonance imaging (MRI) with bone marrow biopsy in diagnosing bone marrow involvement in HD patients. PROCEDURE: Twenty-six patients with the diagnosis of HD were included in this study. The ages of the patients were between 4 and 24 years, with a median of 12. Eleven of them had stage III or IV disease and 15 had been previously diagnosed as having HD and were in relapse. They were evaluated by bone marrow biopsy and MRI of lumbar vertebrae. The biopsies were taken from the anterosuperior iliac spine with an age-appropriate Jamshidi biopsy needle. Within 14 days following biopsy, MRI of lumbar vertebrae was carried out. RESULTS: MRI revealed decreased signal intensity in T1-weighted images in 7 of 26 patients. On the other hand, bone marrow biopsies showed HD involvement in three out of seven patients. The remaining 19 patients who had normal bone MRI were negative for HD in their bone marrow biopsies. The patients with positive MRIs and negative biopsy for HD had bone pain. One of them had a femoral periosteal reaction on bone survey; the other two had height loss in their lumbar vertebral bodies. There was a statistically significant difference in the disease-free survival rates between MRI-positive and -negative patients in the following 24 months period (P < 0.0001). CONCLUSIONS: This study suggests that MRI is a useful method for diagnosing bone marrow involvement in HD, in that our MRI-positive patients had a higher relapse rate in the 24 months follow-up period than the MRI-negative patients.     

MR findings in pituitary haemosiderosis

A girl with Diamond-Blackfan syndrome and hypopituitarism was suspected of having pituitary haemosiderosis because of the clinical picture and the long history of blood transfusions. On T1-weighted MR images the pituitary exhibited a markedly hypointense anterior lobe (mimicking the empty sella), suggesting iron deposition, while on T2W MRI the low signal of the pituitary was surrounded by the high signal of the CSF. MR may be considered the examination of choice for detecting iron overload in the pituitary. Received: 10 November 1997 Accepted: 21 November 1997     

A short protocol for muscle MRI in children with muscular dystrophies

The use of muscle magnetic resonance imaging in patients with muscular dystrophies or congenital myopathies has been limited. We describe the development of a short protocol to be used in young patients with neuromuscular disorders. The protocol includes transverse T1-weighted spin echo sequence images of thighs and calves. The total scanning time is less than 30 minutes, and can be easily applied to patients over the age of 4 years without any need for sedation. Although only the leg muscles are imaged, the images obtained can still help to identify specific patterns of muscle involvement and provide additional help in the differential diagnosis of muscle disorders with overlapping clinical features.     

The value of MRI in early Perthes' disease: an MRI study with a 2-year follow-up

Eleven hips in nine patients with Perthes' disease were studied by plain radiography at 3-month and MRI at 6-month intervals over a period of 2 years. The aim was to clarify the value of MRI in estimating epiphyseal involvement and in predicting uncoverage of the epiphysis. Signal intensities of the epiphysis and metaphysis were visually evaluated from T1- (T1W) and T2-weighted (T2W) images. The extent of decreased signal intensity (DSI) in the epiphyses was volumetrically calculated from T1W images and then compared with follow-up radiographs. The area of epiphyseal DSI corresponding best with Catterall's classification was seen by MRI 3–8 months after the first symptoms. MRI images obtained earlier usually showed less involvement than the follow-up radiographs. However, two features predicting extensive epiphyseal necrosis were: (1) DSI on both T1W and T2W images covering over two-thirds of the epiphysis and (2) diffuse bone marrow oedema of the femoral neck and metaphysis. When T1W images showed a reappearance of high signal intensity patches in the lateral quarter of the epiphysis, no clinically significant uncoverage was seen during the follow-up. Extensive epiphyseal necrosis can, therefore, sometimes be predicted by MRI even within the first 3 months, but MRI visualises epiphyseal involvement more clearly 3–8 months after the first symptoms. Received: 27 March 1996 Accepted: 26 October 1996