Reliability and construct validity of the compatible MRI scoring system for evaluation of elbows in haemophilic children.

We assessed the reliability and construct validity of the Compatible MRI scale for evaluation of elbows, and compared the diagnostic performance of MRI and radiographs for assessment of these joints. Twenty-nine MR examinations of elbows from 27 boys with haemophilia A and B [age range, 5-17 years (mean, 11.5)] were independently read by four blinded radiologists on two occasions. Three centres participated in the study: (Toronto, n = 24 examinations; Atlanta, n = 3; Cuiaba, n = 2). The number of previous joint bleeds and severity of haemophilia were reference standard measures. The inter-reader reliability of MRI scores was substantial (ICC = 0.73) for the additive (A)-scale and excellent (ICC = 0.83) for the progressive (P)-scale. The intrareader reliability was excellent for both P-scores (ICC = 0.91) and A-scores (ICC = 0.93). The total P- and A-scores correlated poorly (r = 0.36) or moderately (r = 0.54), but positively, with clinical-laboratory measurements. The total MRI scores demonstrated high accuracy for discrimination of presence or absence of arthropathy [P-scale, area-under-the-curve (AUC) = 0.94 +/- 0.05; A-scale, AUC = 0.89 +/- 0.06], as did the soft tissue scores of both scales (P-scale, AUC = 0.90 +/- 0.06; A-scale, AUC = 0.86 +/- 0.06). Areas-under-the-curve used to discriminate severe disease demonstrated high accuracy for both P-MRI scores (AUC = 0.83 +/- 0.09) and A-MRI scores (AUC = 0.87 +/- 0.09), but non-diagnostic ability to discriminate mild disease. Similar results were noted for radiographic scales. In conclusion, both MRI scales demonstrated substantial to excellent reliability and accuracy for discrimination of presence/absence of arthropathy, and severe/non-severe disease, but poor to moderate convergent validity for total scores and non-diagnostic discriminant validity for mild/non-mild disease. Compared with radiographic scores, MRI scales did not perform better for discrimination of severity of arthropathy.

Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women.

In this study, total body fat content and fat topography were related to glucose metabolism in the basal and insulin-stimulated states in 18 nonobese and 18 obese premenopausal nondiabetic women. All subjects received a euglycemic insulin (20 mU.min-1.m2) clamp study in combination with [3-3H]-D-glucose infusion and indirect calorimetry to quantitate total body glucose uptake, glucose oxidation, and nonoxidative glucose disposal. Total body fat content was determined with tritiated water, whereas body fat distribution was estimated from the WHR, the STR, and the VSR (measured by magnetic resonance imaging). In the postabsorptive state, total body glucose utilization, glucose oxidation, and nonoxidative glucose disposal rates were similar in nonobese and obese women, whereas during the insulin clamp all three metabolic parameters were reduced significantly in the obese group. In nonobese women, total body fat content was related inversely to both total and nonoxidative glucose disposal during the insulin clamp, whereas no relationship was found between glucose metabolism (total, oxidative, and nonoxidative) and WHR, STR, or VSR. In contrast, in obese women, no relationship was observed between total body fat content and any measure of insulin-mediated glucose metabolism. However, both WHR and VSR were related inversely to total, oxidative, and nonoxidative glucose disposal rates during the insulin clamp. These results suggest that total body fat content and body fat topography are associated differently with insulin-mediated glucose metabolism in nonobese and obese women. In the nonobese women, total body fat mass appears to be a primary determinant of tissue sensitivity to insulin, whereas in obese women, body fat topography exerts a more dominant effect.

Ability of four different techniques of measuring bone mass to diagnose vertebral fractures in postmenopausal women.

Since bone mass has been shown to be an important determining factor of fractures in vitro, we undertook a study to evaluate whether bone mass measurements could separate postmenopausal women with vertebral compression fractures from women of a similar age without fractures. We also wanted to see if methods of measuring bone mass at the spine would be more sensitive or specific than methods that measured bone at the wrist or the entire skeleton. The techniques used were: total body calcium by neutron activation analysis (TBC), single photon absorptiometry (SPA), dual photon absorptiometry (DPA), and quantitative computed tomography (QCT). Normal women aged 20-85 were measured, but only those greater than 50 yr were used in the analysis. Mean values for women with fractures were significantly lower than normals (p less than .001): TBC 642 +/- 103 g vs. 764 +/- 114; SPA .658 +/- .134 g/cm vs. .779 +/- .142; DPA 3.75 +/- .82 g/cm vs. 4.37 +/- .86; QCT 59.0 +/- 25.7 mg/cc vs. 92.6 +/- 36.0. However, each of the methods showed considerable overlap between women with and without fractures. At 90% specificity the sensitivities of the tests were: TBC 34%; SPA 29%; DPA 33%; QCT 36%. When values were expressed as the % expected (based on age and height) then the sensitivities were: TBC 52%; SPA 36%; DPA 35%; QCT 44%. Using Bayes' theorem, we constructed curves showing the posttest probability of these tests at a prevalence of 20%. None of these bone mass measuring techniques showed complete separation between normal and osteoporotic women with fractures; about one-half of the women with fractures were below the normal range. The risk of having a fracture increases as bone mass declines, but our data suggest that bone mass is not the only factor leading to vertebral fractures in postmenopausal women.

Comparisons among methods of measuring bone mass and relationship to severity of vertebral fractures in osteoporosis.

Several techniques are now available for quantitation of bone mass, including total body calcium by neutron activation analysis (TBC), single and dual photon absorptiometry at the radius and spine, respectively (SPA and DPA), quantitative computed tomography of the spine (QCT), and cancellous bone volume from iliac crest bone biopsies. The aims of this study were to assess the correlation among these techniques and to determine if bone mass correlated with height loss or the severity of vertebral fractures in osteoporotic women. These measurements were performed in the same group of women (n = 122) with postmenopausal osteoporosis. TBC, SPA, DPA, and QCT correlated significantly with each other (r = 0.33-0.76). The correlation between QCT and DPA improved significantly (r = 0.33-0.57; P = 0.02) when integral QCT was used instead of the usual QCT of the central vertebra. The correlation was not improved by expressing DPA in different dimensions, but was improved by including normal women. Multiple linear regression analysis showed that TBC was predicted better using SPA, DPA, and QCT than by any single variable. Cancellous bone volume correlated weakly (r = 0.10-0.26) to the other measurements. Height loss and fracture index correlated significantly with each other (r = 0.66; P less than 0.001), but the correlations with bone mass measurements were weak (r = -0.09 to -0.47). For each patient, a bone mass index was defined using z scores from the SPA, DPA, QCT, and TBC measurements; this index correlated inversely with the fracture index (r = -0.29; P = 0.009). This correlation was not significant when controlled for age. Thus, bone mass measurements correlate moderately well with each other, but poorly with severity of fracture. Other factors in addition to low bone mass may be important in determining whether bone will fracture.

Efficacy of long-term fluoride and calcium therapy in correcting the deficit of spinal bone density in osteoporosis.

Long-term fluoride therapy for osteoporosis has been shown to increase the thickness of vertebral trabeculae as seen on spinal radiographs. To determine if this qualitative finding represents a measurable increase in spinal bone density, quantitative computed tomography was utilized to measure trabecular vertebral body density (TVBD) in the lumbar spine of 18 female osteoporotic patients, all of whom had been treated with sodium fluoride, 77 +/- 13 mg/day (mean +/- SD), and calcium, 1000 mg/day, for 57 +/- 24 months. TVBD in these fluoride treated osteoporotic patients (132 +/- 82 mg/cm3) was found to be significantly greater than mean TVBD for an age-matched group of untreated female osteoporotic patients (51 +/- 21 mg/cm3, n = 89, p less than 0.001). The value for TVBD in the long-term fluoride treated osteoporotics was not only similar to previously published values for TVBD (104 +/- 30 mg cm3) in normal females of similar age, but was also above the calculated TVBD "fracture threshold" of 100 mg/cm3 for females. Only one of the 18 fluoride treated osteoporotics continued to have spinal fractures during therapy, accounting for 4 fractures per 87.2 patient years of observation, a value which is significantly lower than the published incidence of 76 fractures per 91 patient years for untreated osteoporotic patients (p less than 0.001). Together, these findings demonstrate that long-term fluoride and calcium therapy for osteoporosis increases TVBD in the majority of patients within a reasonable time frame and significantly reduces the risk for spinal fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Minimal spinal hyperostosis with low-dose isotretinoin therapy.

Skeletal abnormalities have been reported on numerous occasions in patients who have received high doses of vitamin A and its derivatives. Recently, a new derivative, isotretinoin (Accutane, Hoffman-LaRoche, Inc.), has become available for the treatment of cystic acne. Ninety-six patients treated for a minimum of four months with low doses of this drug at two University centers have shown overall good to excellent clinical responses. However, ten of these patients have developed small pointed excrescences on the anterior margins of cervical, thoracic, or lumbar vertebral bodies. The findings are of unknown clinical significance but show some similarities to the spinal findings in DISH syndrome. Follow-up studies will be obtained, but, at the present time, the drug still can be recommended for patients who have severe cystic acne because of the excellent clinical response.

Complications of needle localization of foreign bodies and nonpalpable breast lesions.

Needle-wire localization of foreign bodies and nonpalpable breast lesions is commonly used to allow for more accurate excision or biopsy. We present three examples of complications of the localization procedure: (1) wire migration into the chest wall with retained fragment, (2) transection of a wire during biopsy with retained hook fragment, and (3) wire migration within the thigh soft tissues with breakage at the hooked end. Recommendations to minimize the incidence of these complications and their sequelae include (1) bending the hookwire 90 degree at the skin surface following localization, (2) transferring the patient between the radiology suite and the operating room via a stretcher, with minimal movement of the body part localized, and (3) accounting for the entire length of wire by the surgeon, pathologist, and radiologist following the procedure to exclude retained fragments.

Skeletal hyperostosis in patients receiving chronic, very-low-dose isotretinoin.

BACKGROUND AND DESIGN: We conducted a prospective roentgenographic survey of patients participating in a randomized, placebo-controlled, multicenter clinical trial that evaluated the effectiveness of chronic, very-low-dose (approximately 0.14 mg/kg per day for 3 years) isotretinoin in preventing the subsequent occurrences of new basal cell carcinoma in patients with previous basal cell carcinoma. To assess potential skeletal changes, a sample of 269 patients from among a total of 981 enrollees were randomly selected for comparative roentgenographic review. Baseline and 36-month roentgenograms of the cervical and thoracic spine of each patient were read side by side by a radiologist, masked to treatment group, who noted both the presence and extent of abnormalities at each vertebral level at baseline and the progression of existing or occurrence of new abnormalities at previously unaffected levels at 36 months. RESULTS: In comparison with the placebo group, significantly more patients in the isotretinoin group exhibited progression of existing hyperostotic abnormalities (40% vs 18%; P less than .001) and new hyperostotic involvement at previously unaffected vertebral levels (8% vs 1%; P = .015). CONCLUSION: Our findings indicate that chronic, very-low-dose isotretinoin can induce hyperostotic axial skeletal changes similar to those reported in patients taking higher doses.

Magnetic resonance imaging of musculoskeletal neoplasms.

MRI has been shown to be very useful in the work-up of musculoskeletal neoplasms. The lack of ionizing radiation, the superb contrast resolution, and the ability to directly scan the sagittal and coronal planes make MRI a very attractive imaging mode for treatment planning. With spin-echo MRI, maximum contrast between tumor and fatty tissues generally occurs with short TR and TE times (T1-weighted images). Likewise, maximum contrast between tumor and muscle, tendon, or ligaments occurs with long values of TR and TE (T2-weighted images). Early experience suggests that the already exceptional contrast resolution seen with MRI can be improved even more with the administration of intravenous contrast agents. Just as with CT, fatty tumors can usually be easily distinguished from other tissue types with MRI by means of their differential intensity behavior at different pulse sequences. Fluid-filled tumors, such as unicameral bone cysts or aneurysmal bone cysts may be suspected in the same manner, especially if a fluid-fluid level is seen within the lesion. Otherwise, MRI has not been useful so far in noninvasively determining the histologic type of tumors. Our experience and that of others suggests that MRI is equal or superior to CT in the work-up of musculoskeletal neoplasms. This is especially striking when it is remembered that one is comparing an immature MRI technology with a mature CT technology. Although CT presently has a central role in the staging of musculoskeletal tumors, MRI will shortly supplant it in many cases.

Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound.

Sixty-seven closed or grade-I open fractures of the tibial shaft were examined in a prospective, randomized, double-blind evaluation of use of a new ultrasound stimulating device as an adjunct to conventional treatment with a cast. Thirty-three fractures were treated with the active device and thirty-four, with a placebo control device. At the end of the treatment, there was a statistically significant decrease in the time to clinical healing (86 +/- 5.8 days in the active-treatment group compared with 114 +/- 10.4 days in the control group) (p = 0.01) and also a significant decrease in the time to over-all (clinical and radiographic) healing (96 +/- 4.9 days in the active-treatment group compared with 154 +/- 13.7 days in the control group) (p = 0.0001). The patients' compliance with the use of the device was excellent, and there were no serious complications related to its use. This study confirms earlier animal and clinical studies that demonstrated the efficacy of low-intensity ultrasound stimulation in the acceleration of the normal fracture-repair process.

Evolution of the imaging tests in hemophilia with emphasis on radiography and magnetic resonance imaging.

Even before the discovery of X-rays in 1895 attempts were being made to classify the joint destruction that occurs in hemophilic arthropathy. The advent of radiography added impetus to the search for the optimum classification system. Subsequent attempts have included advanced imaging methods, especially magnetic resonance imaging (MRI). Because of its high spatial resolution and ability to visualize soft tissue abnormalities, MRI is ideally suited as the best way to classify arthropathy. A literature search was carried out to document and list all the imaging methods for hemophilic arthropathy that have been published up to the present. All published classification systems are discussed and listed in tables. MRI has superior imaging capability and will probably become the most important modality for radiological classification of hemophilic arthropathy in the future.

Reliability and construct validity of the compatible MRI scoring system for evaluation of haemophilic knees and ankles of haemophilic children. Expert MRI working group of the international prophylaxis study group.

We tested the reliability and construct validity of the Compatible magnetic resonance imaging (MRI) scale for the evaluation of haemophilic knees and ankles and compared the diagnostic performance of MRI and plain film radiographs. Sagittal and coronal gradient-echo 1.5-T MR images of knees (n=22) and ankles (n=23) were obtained from boys (age range 4-16 years; mean 11 years) in two centres (Toronto, n=26; Europe, n=19). The MR images were independently read by four blinded radiologists on two occasions. Number of previous joint bleedings and laboratory level of severity of haemophilia were the reference standards for imaging assessment. Both components of the MRI scale demonstrated high inter- and intrareader intraclass correlation coefficients (progressive (P) scale, 0.91 and 0.94; additive (A) scale, 0.81 and 0.92 respectively). The correlation between the osteochondral domain of the MRI scale and patient's age was moderate. Otherwise, correlations between A- and P-scales and clinical laboratory measurements were weak. The areas under the curve (AUCs) used for discrimination of disease severity were similar for the A- and P-scales (AUCs used for mild disease, A-scale, 0.72+/-0.07; P-scale, 0.69+/-0.08; P=0.23; AUCs for severe disease, A-scale, 0.93+/-0.05; P-scale, 0.87+/-0.08; P=0.05). No differences were noted between the AUCs of the MRI and radiographic scales used for discrimination of late osteoarticular changes; MRI scales performed better for discrimination of early changes. In conclusion, both MRI scales demonstrated excellent reliability, poor convergent validity, and moderate and excellent validity for discrimination of mild and severe diseases respectively. Compared with radiographic scores, the MRI scales performed better for discrimination of early osteoarticular changes.

Reliability of progressive and additive MRI scoring systems for evaluation of haemophilic arthropathy in children: expert MRI Working Group of the International Prophylaxis Study Group.

Effective treatment of haemophilic arthropathy requires a detailed evaluation of joint integrity. Methodological assessment of magnetic resonance imaging (MRI) scores are needed to assure reproducibility of measurements when comparing results of clinical trials conducted in different centres. We compared the reliability of two MRI scoring systems for assessment of haemophilic arthropathy: one progressive system that displays the most severe change and one additive system that depicts osteochondral and soft tissue-related changes. A total of 47 1.5 T MRI examinations of knees (n = 21) and ankles (n = 26) of 42 haemophilic boys, age range, 22 months to 18 years, performed at different centres (Toronto, n = 20, Europe, n = 12 and Denver, n = 15) were independently reviewed by four radiologists at two occasions. Twenty-two examinations were from children <9 years and 25 from children >/=9. Sagittal and coronal gradient-echo (MPGR, 3D FLASH with fat saturation, GRASS) images were obtained. The MRI examinations of the ankle and knee studies presented with osteochondral abnormalities in 38.5% and 23.8% of the cases respectively. The two scoring systems demonstrated an excellent inter-reader [progressive, 0.88; additive (A, e, s and h components), 0.86] and intra-reader [progressive, 0.92; additive (A, e, s and h components), 0.93] reliability using intraclass correlation coefficients (ICCs). Although ICCs were slightly higher for knees when compared with ankles, and for older children when compared with younger children, all values fell within excellent inter- and intra-reader reliability categories. The two MRI scoring systems demonstrated a comparable reliability. This result constitutes the basis for further development of a combined MRI scoring system for assessment of haemophilic arthropathy, which incorporates progressive and additive components.

Compatible scales for progressive and additive MRI assessments of haemophilic arthropathy.

The international MRI expert subgroup of the International Prophylaxis Study Group (IPSG) has developed a consensus for magnetic resonance imaging (MRI) scales for assessment of haemophilic arthropathy. A MRI scoring scheme including a 10 step progressive scale and a 20 step additive scale with identical definitions of mutual steps is presented. Using the progressive scale, effusion/haemarthrosis can correspond to progressive scores of 1, 2, or 3, and synovial hypertrophy and/or haemosiderin deposition to 4, 5, or 6. The progressive score can be 7 or 8 if there are subchondral cysts and/or surface erosions, and it is 9 or 10 if there is loss of cartilage. Using the additive scale, synovial hypertrophy contributes 1-3 points to the additive score and haemosiderin deposition contributes 1 point. For osteochondral changes, 16 statements are evaluated as to whether they are true or false, and each true statement contributes 1 point to the additive score. The use of these two compatible scales for progressive and additive MRI assessments can facilitate international comparison of data and enhance the accumulation of experience on MRI scoring of haemophilic arthropathy.

Effects of retinoids in bone.

Skeletal effects of retinoids on the spine were studied in two clinical trials. In the first study, spinal radiographs of 96 patients who had been treated with isotretinoin for 4 to 9 months were reviewed. The average age of these patients was 25 years, and during treatment or within 2 1/2 years after the end of treatment, 26% of the patients showed progressive formation of small bony spurs consisting of tiny horizontal excrescences that arose at the anterior margin of one or more vertebral bodies adjacent to the intervertebral disk. In a second study, the radiographs of 241 patients with psoriasis who were treated continually for 1 to 2 years with acitretin were examined. Many of these patients had abnormal radiographs at the start of therapy. These preexisting conditions included psoriatic arthritis, degenerative arthritis, and diffuse idiopathic skeletal hyperostosis. Five percent of the patients showed progression of their abnormalities during the study. The difference in the rate of spur formation in the two groups may be due to multiple factors and not simply to retinoid therapy. Because of the extensive amount of preexisting disease in the psoriasis group compared with the relatively normal appearance of the spine in the isotretinoin group, the underlying disease process may be more important than the retinoid therapy. The development of the spinal spurs was not associated with specific clinical symptoms. Since there was no control group, it is unknown whether the spurs would have developed or progressed in the absence of retinoid therapy.

Hip pain in an adolescent.

We have described a case of osteomyelitis of the ischium with extension into the adjacent soft tissues and abscess formation. Diagnosis and treatment were initially delayed due to the assumption that edema in the thigh muscles seen on initial MRI represented polymyositis. Subsequent radiographs demonstrated a destructive lesion containing a sequestrum within the ischium, indicative of osteomyelitis. It was, however, the MRI imaging that dramatically demonstrated the full extent of the complicating abscess which extended downward to mid-thigh and upward under the gluteal muscles almost to the top of the iliac crest. This proved to be an invaluable guide for the surgeon.

Radiological assessment of haemophilic arthropathy with emphasis on MRI findings.

Medical imaging of haemophilic joints is important for detecting abnormalities, grading their severity and selecting the appropriate therapy. The plain-film scoring systems for staging joint disease that were developed prior to the availability of magnetic resonance imaging (MRI) are inadequate for planning modern prevention and treatment. MRI is capable of delineating all of the soft tissue findings long before they are evident on plain radiographs. In this paper, an MRI scoring system is presented along with examples of joint effusion, haemarthrosis, synovial hypertrophy, haemosiderin deposition, erosions, cysts and cartilage loss. MRI is a powerful tool in the diagnosis, staging and treatment of patients with haemophilic joint disease.