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.

The effects of eccentric velocity on activation of elbow flexors: evaluation by magnetic resonance imaging.

PURPOSE: To compare magnetic resonance imaging (MRI) signal intensity changes in the primary elbow flexors during two isotonic exercise protocols varying in eccentric velocity and the ratio of eccentric to concentric activity. METHODS: Twelve men performed two exercise protocols. The right and left arms were randomly assigned to one of two protocols that had the same workload (60% 1RM) and same total time of exercise (144 s) but differed in the velocity and ratio of eccentric to concentric activity (1:1 and 5:1 for the fast and slow protocols, respectively). MRI signal intensity changes were quantified pre- and post-exercises using an inversion recovery sequence with a 1.5T MRI system (TR = 2500 ms, TE = 90 ms, TI = 140 ms). Percent change in MRI signal intensity, rate of perceived exertion (RPE), and delayed onset muscle soreness (DOMS) were recorded and analyzed. RESULTS: The biceps brachii was found to be preferentially recruited during the fast protocol compared with the brachialis, whereas the brachialis was found to be preferentially recruited during the slow protocol (P < 0.05). The fast exercise protocol was perceived as being more strenuous (RPE = 8.3 +/- 2.1) than the slow (RPE = 5.4 +/- 1.5, P < 0.05) and produced DOMS in 58% of the tested subjects. CONCLUSIONS: These results suggest that agonists respond to various loading conditions nonhomogeneously. These findings may have implications with respect to exercise prescriptions for specific muscles.

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

MRI evaluation of post-operative seromas in extremity soft tissue sarcomas.

OBJECTIVE: To define the spectrum of MRI appearances of postoperative seromas in patients who have undergone excision of extremity soft tissue sarcomas. Local recurrence is always of concern; often a second-look procedure is performed to assess this possibility. Unnecessary surgical exploration may be avoided if radiologists and orthopedic oncologists are familiar with this spectrum of MRI appearances. DESIGN AND PATIENTS: The medical records and images of 85 patients with extremity soft tissue sarcomas were reviewed. Postoperative MRI examinations were available in 46 patients. Eight of these demonstrated MRI evidence of postoperative seroma. The initial size, rate of change, margin, and internal architecture of each seroma was measured, calculated, graded, and graphed. RESULTS AND CONCLUSION: MRI is an excellent modality for the evaluation of postoperative seromas. Globular areas of low to intermediate signal material within seromas may represent organized hematomas or granulation tissue rather than sarcoma recurrence. Local recurrence rarely occurs within seromas.

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.

Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate.

PURPOSE: Urinary retention is a frequently reported complication following radioactive seed implantation of the prostate. If retention is refractory, a post-implant transurethral prostatic resection may ultimately be required to relieve obstruction, leading to an increased risk of urinary incontinence. In this series the incidence of prolonged urinary retention was determined, and the effect of pretreatment and treatment related factors was analyzed to identify high risk patients. MATERIALS AND METHODS: A total of 251 patients with organ confined prostate carcinoma underwent transperineal prostate seed implantation. Of the patients 114 were implanted with 103palladium (103Pd) and 137 with 125iodine seeds. Of the patients who were implanted with 103Pd 90 received 3 months of neoadjuvant hormonal therapy. All patients had International Prostate Symptom Scores (I-PSS) recorded before implantation to assess the degree of urinary symptoms. In the patients receiving neoadjuvant hormones prostate volumes and I-PSS were recorded before initiation of hormone treatment and 3 months later at the time of implant. RESULTS: Urinary retention developed in 14 patients requiring catheterization for more than 48 hours. Median time to onset was 1 day after implant. Of these patients 6 ultimately required transurethral prostatic resection to relieve urinary obstruction. No patient had urinary incontinence following implantation or transurethral prostatic resection. Multivariate analysis revealed that pretreatment I-PSS, and combined treatment with hormonal therapy and 103Pd predicted for the development of retention. Patients with I-PSS 20 or greater had a 29% risk, I-PSS 10 to 19, 11% risk and I-PSS less than 10, 2% risk of retention. Neither patient age, clinical stage, prostate specific antigen, Gleason score, use of 125I nor prostate volume was significant. A subgroup analysis of patients receiving hormonal therapy and 103Pd revealed that those with persistent urinary symptoms (I-PSS 10 or greater) following 3 months of hormonal therapy had the greatest risk of prolonged retention (37%). CONCLUSIONS: The overall risk of prolonged urinary retention following prostate implantation was low in our series. Using the I-PSS questionnaire, high risk patients can be identified before treatment. Patients with significant pretreatment urinary symptoms or persistent urinary symptoms following 3 months of hormonal therapy and then implantation with 103Pd have the greatest risk.

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.

Peroneal tendons: use of kinematic MR imaging of the ankle to determine subluxation.

The purpose of this study was to develop a technique for kinematic MRI of the ankle to evaluate subluxation of the peroneal tendons. A special device was used to perform incremental, passive positioning of the ankle from dorsiflexed to plantarflexed positions for the kinematic MRI examination. A fast spoiled gradient-recalled acquisition in the steady state pulse sequence was used to obtain axial images to assess the peroneal tendons during different positions of the ankle. Seven asymptomatic volunteers and five patients with suspected peroneal tendon subluxation were studied. There was no transverse displacement of the peroneal tendons observed in the asymptomatic subjects nor in two of the patients. Two patients had peroneal tendon subluxation observed on the kinematic MRI studies, and one patient had the peroneal tendons maintained in a displaced position in all ankle positions. The preliminary results suggest that kinematic MRI of the ankle is a potentially useful technique to facilitate evaluation of patients with suspected subluxation of the peroneal tendons, particularly in instances in which subluxation is position-dependent, and spontaneous reduction of the tendons may occur.

A new technique for performing Syed-Neblett template interstitial implants for gynecologic malignancies using transrectal-ultrasound guidance.

PURPOSE: Interstitial brachytherapy plays an important role in the treatment of advanced and recurrent gynecologic malignancies. Unfortunately, the inability to visualize the tumor and surrounding normal structures during the implant has hampered the accuracy and safety of the implant. Transrectal ultrasound guided Syed-Neblett template implantation is a new technique for performing interstitial implants under direct visualization. The details of the technique are presented to demonstrate the ability to accurately guide needle placement into tumor and avoid needle insertion into critical surrounding normal structures. METHODS AND MATERIALS: The transrectal ultrasound is positioned so that it can visualize the tumor, and normal surrounding structures in both transverse and longitudinal planes. The Syed-Neblett template is positioned and sutured into the perineum. Needles are inserted into the target area under direct visualization through transverse imaging. The bladder and rectum can be directly imaged and thus avoided. Longitudinal imaging is then used to guide the needles to the appropriate depth. In addition, it can be used to assess the length of the target volume and aid in determining the active length of the sources. RESULTS: A total of 12 procedures have been performed on seven patients from August 30, 1995 to April 12, 1996. The presenting diseases included: Stage IIIb cervical cancer in four cases, recurrent endometrial cancer in two cases, and Stage III vaginal cancer in one case. The total length of time for implantation of the needles ranged from 45 to 165 min (median--130 min). CONCLUSION: Transrectal ultrasound guidance provides real-time visualization of the target volume and normal tissues during interstitial implantation of gynecologic malignancies and allows for accurate needle placement.

Enhanced radiosensitization with interferon-alpha-2b and cisplatin in the treatment of locally advanced cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy (RT) in the treatment of locally advanced cervical carcinoma. MATERIALS AND METHODS: Twenty-one patients with stage bulky Ib-IIIb (Ib, 2; IIa, 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IFN-alpha (5 million IU) subcutaneously three times per week and cisplatin (25 mg/m2) i.v. infusion over 2 h weekly for 7 weeks, given concomitantly with RT (4500 cGy of external beam plus 2 brachytherapy procedures). Total radiation doses delivered ranged from 7500 to 9960 cGy (median, 9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 months). RESULTS: The 2-year local control rate was 100%. The only sites of disease recurrence were distant. Freedom from distant metastases, disease-free survival, and overall survival at 2 years was 76%. Late complication rates were high. Grade 4 rectosigmoid, bladder, and small bowel complication rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observed 5 to 11.5 months (median, 8 months) after completion of treatment. CONCLUSION: Combination IFN-alpha and cisplatin produced a marked effect of enhanced radiosensitization as evidenced by 100% local tumor control and high late normal tissue complication rates. Due to the unacceptable late toxicity, its routine clinical use cannot be recommended. Further investigation is needed to determine whether a therapeutic window exists such that the use of lower doses of IFN-alpha, cisplatin, or RT can increase tumor control with more acceptable normal tissue toxicity.

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.

Reverse transcriptase-polymerase chain reaction for prostate-specific antigen may be a prognostic indicator in breast cancer.

Among women with node-negative breast cancer and small tumours, it is important to identify those with tumours that will recur, so that they may receive adjuvant therapy, while sparing those with tumours that will not recur the hazards of adjuvant treatment. A reverse transcriptase-polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) may be used to identify circulating metastatic cells in patients with prostate cancer. Approximately 30% of breast cancer cells also produce PSA. Therefore, we tested the PSA RT-PCR assay on blood specimens from women with breast cancer. We evaluated 78 women at Mount Sinai Medical Center with histologically confirmed breast cancer. Venous blood (5 cm3) from the women was collected in ethylene diaminetetraacetic acid (EDTA)-treated collection tubes and approximately 400 ng of RNA from each sample was subjected to an RT-PCR. We were able to detect the amplified PSA fragment in 18 of 78 women with breast cancer; 7 of the 18 women with the PSA fragment had localised, small, node-negative tumours, both oestrogen receptor (ER) positive and ER negative. We could not detect the amplified PSA fragment in 20 normal women and 22 normal men. We conclude that PSA RT-PCR may be a useful method for determining the presence of circulating metastatic cells in some women with node-negative breast cancer, and therefore the potential for these women to develop recurrent disease and thus benefit from adjuvant therapy.

Saline MR peritoneography.

OBJECTIVE: Our objective was to describe a new method for the evaluation of peritoneal surfaces in patients with intraperitoneal carcinomatosis and sarcomatosis. CONCLUSION: Fast spin-echo T2-weighted imaging in conjuction with intraperitoneally instilled saline permits detailed evaluation of peritoneal surfaces, omentum, and mesenteries. The detection of tumor implants is facilitated by their visualization against the saline background. Additionally, normal and abnormal saline distribution patterns can be identified. This technique may also be useful in predicting response to intraperitoneally instilled chemotherapy.