Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders.

Lysosomal storage diseases (LSDs) are a large group of genetic metabolic disorders that result in the accumulation of abnormal material, such as mucopolysaccharides, glycoproteins, amino acids and lipids, within cells. Since many LSDs manifest during infancy or early childhood, with potentially devastating consequences if left untreated, timely identification is imperative to prevent irreversible damage and early death. In this review, the key imaging features of the non-lipid or extralipid LSDs are examined and correlated with salient clinical manifestations and genetic information. Disorders are stratified based on the type of excess material causing tissue or organ dysfunction, with descriptions of the mucopolysaccharidoses, mucolipidoses, alpha-mannosidosis, glycogen storage disorder II and cystinosis. In addition, similarities and differences in radiological findings between each of these LSDs are highlighted to facilitate further recognition. Given the rare and extensive nature of the LSDs, mastery of their multiple clinical and radiological traits may seem challenging. However, an understanding of the distinguishing imaging characteristics of LSDs and their clinical correlates may allow radiologists to play a key role in the early diagnosis of these progressive and potentially fatal disorders.

Response of Gaucher bone disease to enzyme replacement therapy.

In Gaucher disease, enzyme replacement therapy usually reduces liver and spleen volumes and improves haematological abnormalities within 1 year. In contrast, skeletal manifestations of Gaucher disease are thought to respond more slowly. For example, decreased bone marrow glycolipid infiltration and increased bone mineral density have been reported to take up to 3-4 years of treatment. In this report, we present recent studies using T1- and T2-weighted MRI and quantitative chemical shift imaging that demonstrate decreases in abnormal glucocerebroside infiltration and increases in normal fat content of bone marrow within the first year of treatment. There was no obvious relationship between age, gender, splenectomy status or genotype and the response of bone marrow to therapy. Although the dose of enzyme replacement therapy may be related to bone marrow response, no significant relationship was demonstrated in this report. Long-term enzyme replacement therapy induces continued degradation of Gaucher cell deposits, reconversion of fat marrow and increased bone mineral density. This treatment is also associated with improved or non-progressive bone symptoms and functional status in most adult patients, and it prevents the new occurrence of bone pain and bone crisis in nearly all patients. The development of more sensitive, quantitative imaging methods will help to evaluate disease severity better and to assess the response to therapy.

Imaging and quantifying skeletal involvement in Gaucher disease.

Radiological imaging is used in patients with Gaucher disease to estimate the disease burden, to evaluate the presence of specific skeletal complications and to track response to therapy. MRI is currently the best technique for assessing bone marrow involvement in Gaucher disease. Gaucher cell infiltrated bone marrow is characterized by an abnormal low signal intensity on conventional T1- and T2-weighted spin echo sequences, owing to a reduction in fat marrow, which gives a high signal intensity. Enzyme replacement therapy results in a degradation of Gaucher cell deposits with a reconversion of marrow fat and consequently an increased signal on T(1)-weighted images. Conventional MRI also detects other skeletal complications in Gaucher disease, including oedema resulting from acute bone infarction, infection and trauma, avascular necrosis, pathological fractures and vertebral compression. The main drawback of conventional MRI is that it is not quantitative. Quantitative chemical shift imaging is the most sensitive quantitative method for evaluating bone marrow but is not widely available. Alternative MRI-based methods include calculation of the T1 relaxation constant and proton spectroscopy. Scoring of imaging changes detected on conventional MRI may be useful in estimating disease burden and risk of complications. Dual-energy X-ray absorptiometry (DXA) is sensitive to generalized osteopenia and changes in bone mineral density with extended enzyme replacement therapy. However, DXA is insensitive to local changes and cannot yet be used to predict fracture risk in these patients. Until the ideal quantitative technique is developed, conventional MRI will remain the best diagnostic modality for assessing skeletal complications in Gaucher disease and monitoring response to enzyme replacement therapy.

Bone complications in children with Gaucher disease.

For paediatric patients with Gaucher disease, enzyme replacement therapy (ERT) has the potential to prevent the development of serious, irreversible skeletal complications. Analysis of skeletal data for paediatric patients receiving ERT must take into account the pubertal growth spurt and developmental changes in bone marrow composition. In a study conducted at the Burlo Garofolo Institute in Trieste, Italy, 10 paediatric patients have received ERT, and data are available for 3-9 years of follow-up. ERT was associated with a significant increase in the mean lumbar bone mineral density (BMD) Z score after 2 years of treatment (p=0.003). Skeletal growth rates increased among patients exhibiting growth delays. At the Gaucher Disease Treatment Center in Cincinnati, OH, USA, a total of 11 paediatric patients have been followed for 2 years or more of ERT. Of these 11 patients, 6 have demonstrated significant increases in lumbar BMD after 2 years of ERT; these patients tended to have lower BMD Z scores at the start of ERT. At the Children's Hospital of the Johannes-Gutenberg University in Mainz, Germany, 7 children with type 1 Gaucher disease presented with reduced BMD in the distal ulna, and after 18-24 months of ERT, these patients demonstrated increases in BMD at this site. The patients exhibiting growth retardation experienced growth acceleration during treatment. These studies suggest that ERT improves BMD and growth rates in paediatric patients with Gaucher disease. ERT in paediatric patients may have the potential to prevent serious skeletal complications such as fractures and vertebral compression later in life.

Bone marrow response in treated patients with Gaucher disease: evaluation by T1-weighted magnetic resonance images and correlation with reduction in liver and spleen volume.

PURPOSE: To determine whether T1-weighted magnetic resonance (MR) images can demonstrate response in the marrow of patients with type 1 Gaucher disease treated with enzyme replacement therapy (ERT) and to determine whether a relationship exists between liver and spleen volume reductions and visible marrow changes. PATIENTS: Forty-two patients with type 1 Gaucher disease were evaluated on at least two occasions. Thirty-two patients received ERT. Of these patients, 15 had a baseline examination prior to the initiation of ERT. The remaining 10 patients did not receive ERT. DESIGN: T1-weighted and gradient recalled echo (GRE) coronal images of the femurs and hips were obtained. Concurrently, liver and spleen volumes were determined using contiguous breath-hold axial gradient-echo images. T -weighted images of the hips and femurs were evaluated to determine change or lack of change in the yellow marrow. RESULTS: Of the 32 patients receiving ERT, 14 (44%) demonstrated increased signal on T1-weighted images suggesting an increase in the amount of yellow marrow. If only the 15 patients with a baseline examination were considered, the response rate to ERT was 67%. Using Student's t-test a highly significant correlation (P<0.005) was found between marrow response and reduction in liver and spleen volume. CONCLUSIONS: Marrow changes in patients receiving ERT can be detected by T -weighted images. This response correlated with reductions in visceral volumes (P<0.0005).

MRI of destructive achilles tendon rupture associated with skin ulceration.

We present a case series of the MR findings of destructive tears of the Achilles tendon secondary to overlying soft tissue ulcerations.

Diagnosis of vertebral metastasis, epidural metastasis, and malignant spinal cord compression: are T(1)-weighted sagittal images sufficient?

The objective of this study was to determine whether T(1)-weighted sagittal images alone are adequate in the diagnosis of vertebral metastasis, epidural metastasis, and malignant spinal cord compression. Ninety-four complete magnetic resonance (MR) studies of the spinal column (a complete study consisting of T(1)-weighted sagittal images, T(2)-weighted sagittal images, and T(1)- and/or T(2)-weighted axial images) and 94 T(1)-weighted sagittal images alone (a subset of the complete studies) from 57 consecutive cancer patients over the last 2 years with clinically suspected cord compression were blindly and independently evaluated by four radiologists. The complete MR studies were used as the standard. Overall, the sensitivity of T(1)-weighted sagittal images alone to vertebral metastasis (87%) was statistically greater than cord compression (70%) (p = 0.05), and statistically greater than epidural metastasis (46%) (p

Dual oblique MR method for imaging the sciatic nerve.

We present an alternative imaging technique for evaluation of the sacral plexus and sciatic nerve. Images were obtained in the oblique coronal, oblique sagittal, and oblique axial planes using the piriformis muscle as the initial reference point. Evaluation of the sciatic nerve is optimized by the multiplanar capability of MRI.

Gadolinium-enhanced MR imaging of traumatic hepatic injury.

OBJECTIVE: Our objective was to evaluate the use of contrast-enhanced MR imaging in the examination of a limited number of patients with hepatic trauma who had also undergone CT. CONCLUSION: The conspicuity of most lesions was better on contrast-enhanced MR imaging than on unenhanced MR imaging. Also, conspicuity on contrast-enhanced MR imaging was at least subjectively equivalent to that on CT.

Injury of the posterior ligament complex in patients with acute spinal trauma: evaluation by MR imaging.

OBJECTIVE: We undertook this study to use MR imaging to determine the frequency of injury to the posterior ligament complex of the thoracolumbar spine in patients who have undergone acute thoracolumbar trauma. SUBJECTS AND METHODS: Sixty-eight patients with varying severity of thoracolumbar trauma were examined prospectively. The majority of injuries were related to motor vehicle accidents. The second most common cause was falls. Patients were examined with plain radiography and MR imaging. In addition to conventional MR imaging sequences consisting of T1-weighted and fast spin-echo T2-weighted sagittal and axial images, a fat-suppressed T2-weighted sagittal sequence was performed. The findings were correlated with surgery in six cases and with follow-up clinical examination that included physical examination and conventional anteroposterior and lateral radiographs. RESULTS: Posterior ligament complex injury was detected in 53% (n = 36) of all patients. Such injury was most common in patients with flexion-distraction (n = 15) and patients with dislocation fracture (n = 4). Of the patients with dislocation fracture, all had posterior ligament complex injury. Of the 24 patients with burst fractures, posterior ligament complex tear occurred in 42% (n = 10). Of the 23 patients with compression fractures, 26% (n = 6) had posterior ligament complex tear. Injury to the interspinous ligaments occurred with decreasing frequency in patients with injury to the supraspinous ligament, flaval ligaments, posterior longitudinal ligament, and anterior longitudinal ligament. Surgical findings correlated with MR imaging in all six patients who underwent surgery. CONCLUSION: Injury to the posterior ligament complex, which is often encountered in patients with burst and compression fractures, can be reliably revealed by MR imaging.

Magnetic resonance imaging to detect avascular necrosis after open reduction and internal fixation of talar neck fractures.

Twenty-one consecutive patients with displaced talar neck fractures (12 Hawkins type II, 9 Hawkins type III) were prospectively evaluated with magnetic resonance (MR) scans performed between 3 days and 12 months after surgery. All patients underwent open reduction and internal fixation with titanium screws, except two who underwent fixation with stainless steel implants that were subsequently removed. All patients had plain radiographs. We classified the scans as follows: type A, no abnormal signal changes in the body of the talus; type B, signal changes in less than 25% of the body; type C, signal changes in 25% to 50% of the body; and type D, signal changes in greater than 50% of the body. Plain anteroposterior radiographs correlated well with MR scans in patients with type D scans, but an inconsistent correlation was noted with lesser degrees of signal changes (types A-C), with the MR scans being more accurate in displaying the volume of avascular bone. Scans obtained less than 3 weeks after injury were not helpful in assessing for avascular necrosis. We found that high-quality MR images of the talus were consistently obtained in the presence of titanium screws in contrast to images obtained with stainless steel implants. We use titanium screws in all talar neck fracture repairs, because they permit high-quality MR images. We believe that further study of patients with Hawkins type III fractures and Hawkins type II fractures with equivocal radiographic evidence of avascular necrosis is warranted to try to identify those patients at risk for collapse and perhaps to guide weightbearing recommendations.

Magnetic resonance angiography in neck masses.

Carotid MR angiography has primarily been used to evaluate for stenotic lesions. We performed 2D time of flight MR angiography in 25 patients with palpable neck masses. There were 23 masses confirmed histologically. Two of the masses represented abnormal carotid arteries. Carotid deviation was seen in 23 of 25 (92%) of patients. Widening of the carotid bifurcation was identified in seven patients, including four carotid body tumors, one inflammatory mass, one benign salivary gland tumor, and one schwannoma. Increased vascularity was identified in one carotid body tumor and in one metastatic papillary carcinoma of the thyroid. MR angiography may be useful to demonstrate flow within vessels and represents a familiar imaging display for surgical planning. Splaying of the carotid bifurcation is useful in demonstrating carotid space lesions.

MR findings in patients with acute tibial plateau fractures.

OBJECTIVE: The purpose of this study was to demonstrate the MRI findings associated with acute tibial plateau fractures. MATERIALS AND METHODS: MR scans of 29 patients with acute tibial plateau fractures were analyzed retrospectively. The images were evaluated for the presence of injuries involving the menisci, cruciate and collateral ligaments. The presence of a lipohemarthrosis or a simple joint effusion was also noted. The tibial plateau fractures were classified according to the scheme devised by Schatzker. RESULTS: Evidence of internal derangement of the knee was found in 28 (97%) patients. Tibial collateral ligament (55%) injuries and lateral meniscus (45%) tears were noted most frequently. Medial meniscus tears were seen in 21% and fibular collateral ligament injuries were diagnosed in 34%. Forty-one percent had anterior cruciate ligament injuries while the posterior cruciate ligament was injured in 28%. Twelve (41%) patients demonstrated the characteristic MRI features of a lipohemarthrosis. Simple joint effusions were found in the remaining 17 (59%) patients. CONCLUSION: MR imaging in patients with acute tibial plateau fractures commonly demonstrates associated ligamentous and meniscal injuries. By imaging in multiple planes, MRI can aid in the accurate characterization of tibial plateau fracture patterns and severity.

The application of magnetic resonance techniques to the evaluation of the patient with sickle-cell disease.

Sickle-cell anemia presents unique challenges to the clinician who wishes to obtain important data regarding anatomic lesions and metabolic states without subjecting the patient to additional risks involving the imaging techniques. Two applications-magnetic resonance angiography and magnetic resonance spectroscopy-are described in this review.

Magnetic resonance imaging applications to cardiac diagnosis.

Applications of MRI to cardiac diagnosis have improved and expanded. Thus, while MRI was initially useful for demonstrating cardiac anatomy, congenital malformations, thrombi, and masses, current techniques can demonstrate cardiac function, including evaluation of valvular disease and cardiac shunts along with cardiac flow quantitation. Further refinements have led to the demonstration of coronary artery anatomy. In the future, a comprehensive cardiovascular evaluation may be available with MRI.

Method for assessing cardiac function using magnetic resonance imaging.

The authors sought to define a method to use magnetic resonance (MR) to assess cardiac function by obtaining short-axis images of the left ventricle (LV) in humans. Sagittal and axial scout1H MR images were used in the protocol. The long axis of the LV was defined in both planes using the mitral valve and left ventricular apex as references. Based on this double angulation, the acquisition planes were created for a series of parallel short-axis images extending from the base to the apex of the left ventricular cavity. Cardiac images acquired with a fast-field echo technique, six slices with 16-20 phases per RR interval, were analyzed, representing the initial 75-80% of the cardiac cycle. For each slice, the endocardial border of the left ventricular chamber was manually traced. Using Simpson's rule, the total LV volume at a given phase was determined, considering the traced area, thickness, and position in three-dimensional space of each of the six constituent slices. The calculated volumes were plotted against time, and the stroke volume, ejection fraction, and cardiac output were determined. These parameters are clinically significant indices of cardiac function. Accurate and useful estimates of LV function can be obtained using MRI according to this protocol.

The impact on treatment planning of MRI of the spine in patients suspected of vertebral metastasis: an efficacy study.

The objective of this study was to determine the efficacy of spinal MRI in suspected spinal metastasis. The effect of spinal MRI on treatment planning choices (radiation, chemotherapy, steroids, or surgery) in 130 patients with suspected spinal metastatic involvement was evaluated. In a retrospective group of 100 patients, 47 (47%) had therapy changes associated with MR findings. Forty out of 78 (51%) of patients presenting with symptoms (back pain, weakness, paresthesia, or sphincter dysfunction) had MR associated therapy choices. Seven out of 22 (32%) of patients without spinal symptoms had therapy changes. Twelve out of 30 (40%) of patients evaluated prospectively had therapy choices directed by MR findings. Overall, 59 out of 130 (45%) of patients had therapy choices associated with findings in spinal MRI. MRI results influenced the addition or modification of radiation therapy treatment in 33% of the patients suspected of metastatic disease to the spine.

Magnetic resonance imaging of acute Maisonneuve fractures.

Magnetic resonance imaging (MRI) studies were performed on five patients with acute Maisonneuve fractures. All patients had sustained a twisting injury to their ankles and complained of ankle pain and pain over their proximal fibula. High quality images with excellent visualization of all the ankle ligamentous structures were obtained. MRI showed that the anterior inferior tibiofibular ligament was disrupted in all patients and the posterior inferior tibiofibular ligament was intact in three of five patients. Also, the anterior talofibular ligament was disrupted in all patients and the calcaneofibular ligament was ruptured in two of five patients. This raises the question of whether patients with Maisonneuve fractures have lateral ankle instability at long-term follow-up. Although the superficial deltoid ligament was disrupted in all patients, the deep deltoid ligament was intact in one patient, partially disrupted in one patient, and completely disrupted in three patients. The interosseous ligament was disrupted at the ankle in all patients, while the interosseous membrane was disrupted in the leg in all patients except one. This patient had an intact interosseous membrane despite rupture of the interosseous ligament at the ankle and the presence of a proximal one third fibula fracture.

MR imaging of patients with type 1 Gaucher's disease: relationship between bone and visceral changes.

OBJECTIVE: Because treatment is now available for patients with Gaucher's disease, methods of follow-up have become important in making treatment decisions. Bone abnormalities (infarct and avascular necrosis) tend to be irreversible while visceral volumes are not, suggesting that it may be useful to follow patients with visceral volume determinations. In order to do so, the relationship of one to the other must first be understood. The purpose of this paper is to determine the relationships between bone and visceral changes identified with MR imaging. MATERIALS AND METHODS: Sixty-two consecutive patients from 1 to 78 years old with type 1 Gaucher's disease were studied by MR imaging. The examination consisted of two parts: T1-weighted MR images and gradient-echo coronal MR images of the hips and femurs, and axial breath-holding MR images of the abdomen that allowed measurement of hepatic and splenic volume. The bone changes were classified and were correlated with the liver and spleen volumes. Specific imaging features of the liver and spleen were noted and correlation sought. RESULTS: A statistically significant difference in liver size was found between patients with and without avascular necrosis. A statistically significant correlation was also found between liver size and avascular necrosis. Patients with marrow changes classified as grade 2 or higher were significantly more likely to have avascular necrosis. Nineteen percent of patients had splenic nodules and 7% had hepatic nodules; however, there was no correlation between the nodules and bone changes. CONCLUSION: MR imaging showed a statistical relationship between marrow changes, liver size, and avascular necrosis in patients with type 1 Gaucher's disease. Knowledge of this relationship may be used in dosage and treatment considerations in the follow-up and clinical management of these patients.