OARSI Clinical Trials Recommendations: Knee imaging in clinical trials in osteoarthritis.

Significant advances have occurred in our understanding of the pathogenesis of knee osteoarthritis (OA) and some recent trials have demonstrated the potential for modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply knee imaging in knee OA trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for magnetic resonance imaging (MRI)); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance (QA)/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations.

Quantitative 3D MRI reveals limited intra-lesional bony overgrowth at 1 year after microfracture-based cartilage repair.

OBJECTIVE: Intra-lesional bony overgrowth (BO) identified during or following cartilage repair treatment is being frequently described through subjective reports focusing primarily on incidence. Our objective was to quantify the exact volume of intra-lesional BO at 12 months post-cartilage repair treatment, to determine if a correlation exists between the extent of BO and clinical outcomes, and to visualize and characterize the BO. DESIGN: MRI scans were systematically obtained during a randomized clinical trial for cartilage repair (Stanish et al., 2013) that compared two microfracture-based treatments in 78 patients. Semi-automated morphological segmentation of pre-treatment, 1 and 12 months post-treatment scans utilizing a programmed anatomical atlas for all knee bone and cartilage structures permitted three-dimensional reconstruction, quantitative analysis, as well as qualitative characterization and artistic visualization of BO. RESULTS: Limited intra-lesional BO representing only 5.8 ± 5.7% of the original debrided cartilage lesion volume was found in 78 patients with available MRIs at 12 months. The majority (80%) of patients had very little BO (<10%). Most occurrences of BO carried either spotty (56.4%) or planar (6.4%) morphological features, and the remaining balance (37.2%) was qualitatively unobservable by eye. Pre-existing BO recurred at 12 months in the same intra-lesional location in 36% of patients. No statistical correlations were found between BO and clinical outcomes. CONCLUSIONS: Intra-lesional BO following microfracture-based treatments may not be as severe as previously believed, its incidence is partly explained by pre-existing conditions, and no relationship to clinical outcomes exists at 12 months. Morphologically, observable BO was categorized as comprising either spotty or planar bone.

The effect of anterior cruciate ligament injury on bone curvature: exploratory analysis in the KANON trial.

OBJECTIVE: Investigate the 5-year longitudinal changes in bone curvature after acute anterior cruciate ligament (ACL) injury, and identify predictors of such changes. METHODS: In the KANON-trial (ISRCTN 84752559), 111/121 young active adults with an acute ACL tear to a previously un-injured knee had serial 1.5 T MR images from baseline (within 5 weeks from injury) to 5 years after injury. Of these, 86 had ACL reconstruction (ACLR) performed early or delayed, 25 were treated with rehabilitation alone. Measures of articulating bone curvature were obtained from computer-assisted segmentation of MR images. Curvature (mm(-1)) was determined for femur, tibia, medial/lateral femur, trochlea, medial/lateral tibia. Age, sex, treatment, BMI, meniscal injury, osteochondral fracture on baseline MR images were tested for association. RESULTS: Over 5 years, curvature decreased in each region (P < 0.001) suggesting flattening of convex shapes and increased concavity of concave shapes. A higher BMI was associated with flattening of the femur (P = 0.03), trochlea (P = 0.007) and increasing concavity of the lateral tibia (LT) (P = 0.011). ACLR, compared to rehabilitation alone, was associated with flatter curvature in the femur (P < 0.001), medial femoral condyle (P = 0.006) and trochlea (P = 0.003). Any meniscal injury at baseline was associated with a more flattened curvature in the femur (P = 0.038), trochlea (P = 0.039), lateral femoral condyle (P = 0.034) and increasing concavity of the LT (P = 0.048). CONCLUSION: ACL injury is associated with significant changes in articulating bone curvature over a 5 year period. Higher BMI, baseline meniscal injury and undergoing ACL reconstruction (as distinct from undergoing rehabilitation alone) are all associated with flattening of the articulating bone.

Region of interest analysis: by selecting regions with denuded areas can we detect greater amounts of change?

INTRODUCTION: Based on recent analyses, the measures of short-term responsiveness of magnetic resonance imaging (MRI) derived cartilage morphometry may not be as large as earlier studies had suggested. We examined if by selecting regions of interest with denuded cartilage, the remaining cartilage within this region of interest was susceptible to greater rates of cartilage loss. METHODS: Subjects included for this analysis are a subset of the approximately 4700 participants in the Osteoarthritis Initiative (OAI) Study. Bilateral radiographs and 3T MRI (Siemens Trio) of the knees and clinical data are obtained at baseline and annually in all participants. Hundred and fifty subjects from the OAI progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic osteoarthritis (ROA defined as definite tibio-femoral osteophytes on X-ray) based on a screening reading done at the OAI clinics. One knee from each subject was selected for analysis. Using sagittal 3D DESSwe MR images from the baseline and 12-month follow-up visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalized cartilage volume (volume normalized to bone surface interface area), and percent denuded area (Total Cartilage Bone Interface area denuded of cartilage). Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardized response mean (SRM), i.e., mean change divided by the standard deviation (SD) of that change were calculated. Analyses are stratified into three groups according to baseline assessment of denuded area: those with no denuded area in the region of interest at baseline, and then two groups (intermediate denuded area (or=median) denuded area) of equal sample size. RESULTS: On average the subjects were 60.9 years of age and obese with a mean body mass index (BMI) of 30.3 kg/m(2). For the combined central medial femur and tibia the mean volume change for the whole sample was -48.2 (SD 159.8) mm(3), which gives an SRM of -0.30. In the subsample of knees with no denuded area the SRM was -0.25, in the knees with intermediate denuded area the SRM was -0.30, and in knees with severe denuded area the SRM was -1.00. For normalized volume of the central medial femur in the subsample of knees with no denuded area the SRM was -0.22, in the knees with intermediate denuded area the SRM was -0.26, and in knees with severe denuded area (n=23) the SRM was -0.71. The magnitude of the SRMs was generally smaller in participants with no denuded area. In contrast, the SRMs in participants with denuded area were larger. CONCLUSION: By selecting participants with the presence of cartilage regions with denuded area the ability to demonstrate change in cartilage loss in that specific location is markedly improved compared to persons without a full thickness lesion in that cartilage plate. This option for screening during recruitment in clinical trials could facilitate the detection of participants at greater risk of subsequent cartilage loss.

Change in cartilage morphometry: a sample of the progression cohort of the Osteoarthritis Initiative.

OBJECTIVE: The performance characteristics of hyaline articular cartilage measurement on magnetic resonance imaging (MRI) need to be accurately delineated before widespread application of this technology. Our objective was to assess the rate of natural disease progression of cartilage morphometry measures from baseline to 1 year in knees with osteoarthritis (OA) from a subset of participants from the Osteoarthritis Initiative (OAI). METHODS: Subjects included for this exploratory analysis are a subset of the approximately 4700 participants in the OAI Study. Bilateral radiographs and 3T MRI (Siemans Trio) of the knees and clinical data were obtained at baseline and annually in all participants. 160 subjects from the OAI Progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic OA based on a screening reading done at the OAI clinics were eligible for this exploratory analysis. One knee from each subject was selected for analysis. 150 participants were included. Using sagittal 3D DESSwe (double echo, steady-state sequence with water excitation) MR images from the baseline and 12 follow-up month visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalised cartilage volume (volume normalised to bone surface interface area), and percentage denuded area (total cartilage bone interface area denuded of cartilage). RESULTS: Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardised response mean (SRM), ie, mean change divided by the SD change were calculated. On average the subjects were 60.9 years of age and obese, with a mean body mass index of 30.3 kg/m2. The SRMs for cartilage volume of various locations are: central medial tibia -0.096; central medial femur -0.394; and patella -0.198. The SRMs for normalised cartilage volume of the various locations are central medial tibia -0.044, central medial femur -0.338 and patella -0.193. The majority of participants had a denuded area at baseline in the central medial femur (62%) and central medial tibia (60%). In general, the SRMs were small. CONCLUSIONS: These descriptive results of cartilage morphometry and its change at the 1-year time point from the first substantive MRI data release from the OAI Progression subcohort indicate that the annualised rates of change are small with the central medial femur showing the greatest consistent change.

The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year.

OBJECTIVES: To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS: Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS: JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION: Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.

The effect of etanercept on osteoclast precursor frequency and enhancing bone marrow oedema in patients with psoriatic arthritis.

OBJECTIVE: The frequency of osteoclast precursors (OCPF) and the presence of bone marrow oedema (BMO) are potential response biomarkers in psoriatic arthritis (PsA). Previous studies suggest a central role for tumour necrosis factor (TNF) in the formation of osteoclast precursors. To better understand this association, the effect of etanercept on OCPF and BMO was analysed in PsA patients with erosive arthritis. METHODS: A total of 20 PsA patients with active erosive PsA were enrolled. Etanercept was administered twice weekly for 24 weeks. OCPF was measured and clinical assessments were performed at baseline, 2, 12 and 24 weeks. Gadolinium enhanced MR images were obtained at baseline and 24 weeks. RESULTS: Significant improvements in joint score (p<0.001), HAQ scores (p<0.001) and SF-36 parameters were observed after 6 months of therapy with etanercept compared to baseline. The median OCPF decreased from 24.5 to 9 (p = 0.04) and to 7 (p = 0.006) after 3 months and 6 months of treatment, respectively. MR images were available for 13 patients. The BMO volume decreased in 47 and increased in 31 sites at 6 months. No correlation was noted between OCPF, BMO and clinical parameters. CONCLUSION: The rapid decline in OCPF and overall improvement in BMO after anti-TNFalpha therapy provides one mechanism to explain the anti-erosive effects of TNF blockade in PsA. Persistence of BMO after etanercept treatment, despite a marked clinical response, was unexpected, and suggests ongoing subchondral inflammation or altered remodelling in PsA bone.

Utility of creatinine excretion in body-composition studies of healthy men and women older than 60 y.

This study evaluated whether aging alters the usefulness of creatinine excretion as an index of lean body mass (LBM) or muscle mass in healthy men and women. Creatinine excretion was determined while 24 young (15 men and 9 women aged < 32 y) and 38 older (23 men and 15 women aged > 60 y) healthy volunteers stayed at a clinical research center for 3 d. Total LBM was determined by 40K counting in all subjects, and cross-sectional areas of upper arm and thigh muscles were determined in some subjects (10 young, 20 old) by magnetic resonance imaging. The slopes and intercepts of the regression equations relating LBM to average daily creatinine excretion were the same in the younger and older groups, and the precision with which LBM could be determined from creatinine excretion was not diminished by aging. Creatinine excretion was closely correlated with cross-sectional areas of upper arm (r = 0.85) and thigh (r = 0.88) muscles, and the slopes and intercepts of the regression equations were not significantly affected by age. The older group had a mean LBM smaller than that of the younger group, which was accounted for entirely by a smaller muscle mass. Mean resting metabolic rate (RMR), whole-body protein turnover rate, and thigh strength were lower in the older group than in the young group. Adjustment of RMR and protein turnover for creatinine excretion or LBM eliminated the age effects. Strength was lower in the older group even after adjustment for creatinine excretion or LBM. This study indicates that creatinine excretion is useful for evaluating body composition in both young and old subjects.

MR image-guided portal verification for brain treatment field.

PURPOSE: To investigate a method for the generation of digitally reconstructed radiographs directly from MR images (DRR-MRI) to guide a computerized portal verification procedure. METHODS AND MATERIALS: Several major steps were developed to perform an MR image-guided portal verification procedure. Initially, a wavelet-based multiresolution adaptive thresholding method was used to segment the skin slice-by-slice in MR brain axial images. Some selected anatomical structures, such as target volume and critical organs, were then manually identified and were reassigned to relatively higher intensities. Interslice information was interpolated with a directional method to achieve comparable display resolution in three dimensions. Next, a ray-tracing method was used to generate a DRR-MRI image at the planned treatment position, and the ray tracing was simply performed on summation of voxels along the ray. The skin and its relative positions were also projected to the DRR-MRI and were used to guide the search of similar features in the portal image. A Canny edge detector was used to enhance the brain contour in both portal and simulation images. The skin in the brain portal image was then extracted using a knowledge-based searching technique. Finally, a Chamfer matching technique was used to correlate features between DRR-MRI and portal image. RESULTS: The MR image-guided portal verification method was evaluated using a brain phantom case and a clinical patient case. Both DRR-CT and DRR-MRI were generated using CT and MR phantom images with the same beam orientation and then compared. The matching result indicated that the maximum deviation of internal structures was less than 1 mm. The segmented results for brain MR slice images indicated that a wavelet-based image segmentation technique provided a reasonable estimation for the brain skin. For the clinical patient case with a given portal field, the MR image-guided verification method provided an excellent match between features in both DRR-MRI and portal image. Moreover, target volume could be accurately visualized in the DRR-MRI and mapped over to the corresponding portal image for treatment verification. The accuracy of DRR-MRI was also examined by comparing it to the corresponding simulation image. The matching results indicated that the maximum deviation of anatomical features was less than 2.5 mm. CONCLUSION: A method for MR image-guided portal verification of brain treatment field was developed. Although the radiographic appearance in the DRR-MRI is different from that in the portal image, DRR-MRI provides essential anatomical features (landmarks and target volume) as well as their relative locations to be used as references for computerized portal verification.

Magnetic resonance imaging of deep vein thrombi correlates with response to thrombolytic therapy.

Fibrinolytic therapy can result in rapid lysis of deep vein thrombi (DVT), but its use is limited by the failure of many patients to respond and by the increased risk of bleeding complications in comparison with anticoagulant therapy alone. Treatment could be improved by the ability to select patients most likely to respond. Since magnetic resonance (MR) imaging may be sensitive to thrombus age and structure, properties related to thrombolytic sensitivity, we have evaluated the ability of MR imaging to predict the response of DVT to thrombolytic therapy. Nine patients with venographically documented proximal DVT were treated with streptokinase, and MR imaging using a gradient recall echo sequence was performed before and after therapy. The proximal leg veins were divided into nine segments in each patient, and thrombus was present in 55 segments. The MR appearance of the thrombus in each segment was evaluated prior to therapy, and the amount of clot lysis was determined by comparing pre- and post-treatment MR images. MR imaging accurately identified thrombus in all cases in comparison with venography and also identified proximal extension into pelvic veins that was not identified venographically. Prior to treatment, the thrombus in eight of nine patients varied in appearance in different vein segments consistent with a course of progressive extension over time. Thrombi with low MR signal occurred more often in patients with symptoms of four days or less, and were also more common in partially occluded segments (10/12, 83%) than with total occlusion (7/43, 16%) (p < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of two warfarin regimens in the prevention of venous thrombosis following total knee replacement.

A prospective, randomized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement. Adult patients scheduled for primary or revision total knee replacement were randomly assigned to receive either a "two-step" warfarin regimen beginning 10-14 days pre-operatively or, alternatively, to begin warfarin the night before surgery. Post-operatively, the dose was adjusted in both groups to achieve a target International Normalized Ratio (INR) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. The occurrence of deep vein thrombosis was nearly the same in the two treatment groups, 39% in patients randomized to the two-step regimen as compared to 38% in those beginning the night before surgery. The occurrence of proximal vein thrombosis was also similar, 5% versus 7% (p = NS). Patients in the two-step group received 1.33 +/- 1.26 transfusions compared to 0.95 +/- 1.22 in the night before group (p < 0.05) and also had a lower nadir post-operative hematocrit of 26.7 +/- 3.1 as compared to 28.5 +/- 3.2 (p < 0.0001). Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group. Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis. We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10-14 days pre-operatively. Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications.

Effects of the magnetic resonance contrast medium ferrioxamine methanesulfonate on systemic and renal hemodynamics in the anesthetized dog.

Ferrioxamine methanesulfonate (S-FDF) is a new magnetic resonance (MR) contrast agent developed to improve magnetic resonance imaging of the abdomen and pelvis. This stable complex of deferoxamine methanesulfonate and iron is excreted in the urine by glomerular filtration modified by active renal tubular resorption. This study examines the acute systemic and renal hemodynamic responses to this agent after intravenous administration either as an infusion of 25 mg/kg over 5 minutes or as a rapid bolus at a dose of 50 mg/kg. In eight anesthetized dogs, renal plasma flow (RPF) was measured with an electromagnetic flowmeter, and GFR was determined by the renal extraction of technetium-99m-DTPA. Mean arterial pressure (MAP), pulse rate, and a lead II ECG were assessed. At a dose of 25 mg/kg over 5 minutes, MAP decreased significantly (control 146.0 +/- 6.5 mm Hg vs. 107 +/- 18 mm Hg at 2 minutes; P less than .05). In two of the eight animals, the MAP dropped below 60 mm Hg. Significant decreases in GFR and RPF also were noted. All four of the animals receiving the rapid injection of S-FDF experienced profound hypotension (MAP less than 50 mm Hg). The drop in heart rate from 152 +/- 11.6 bpm to 121 +/- 4.9 bpm was associated with a marked depression of the ST wave in the lead II ECG. Further animal studies are needed to assess the mechanism of toxicity and a potential synergism of action with pentobarbital anesthesia.

Intramuscular myxoma--a clinicopathological study of twenty-three cases.

Twenty-three cases of intramuscular myxoma were analyzed clinically and histologically. The mean age of the patients was 54 years, and two-thirds were women. Clinical follow-up of 2 to 17 years' duration revealed no recurrences or metastases. Intramuscular myxoma thus appears to be a completely benign tumor. One patient simultaneously had a myxoma in the muscle of the thigh and a lesion of fibrous dysplasia in the femur. In addition, 14 of 16 patients studied with x-ray had a significantly higher incidence of minor abnormalities in bones as compared with the normal population. The myxomas were characterized histologically by sparse cellularity, abundant intercellular material digestible with hyaluronidase, and lack of mitotic figures. At the ultrastructural level, the tumor cells showed characteristics of fibroblasts and myofibroblasts. Immunohistochemical analysis of intermediate filament proteins revealed vimentin- but no desmin-positivity in the tumor cells, and endothelial cell markers as well as S-100 protein were absent. This is compatible with fibroblastic-myofibroblastic nature of the myxoma cells.

The desmoid tumor. II. Analysis of factors possibly contributing to the etiology and growth behavior.

Eighty histologically verified cases of the desmoid tumor (DT) have been analyzed with regard to factors possibly contributing to the etiology and/or growth behavior of this uncommon neoplasm. Considering the four statistical age components, the "fertile" female and "menopausal" varieties of the DT grew distinctly faster (0.1 less than P greater than 0.05 and less than 0.05), and the female "juvenile" variety distinctly slower (0.1 less than P greater than 0.05) than the male DTs. In a visual estimate, the fertile female patients had a significant (P less than 0.01) predisposition to estrogen predominance, while fewer patients than expected displayed progesterone predominance or were at balance (P = NS and less than 0.01, respectively). Thirty-two per cent of the patients with an abdominal DT had been previously operated in the region of subsequent tumor growth. Significantly more pregnancies were observed in patients with abdominal DT than with extra-abdominal DT (P less than 0.05). On only one occasion did sigmoideoscopy reveal colonic polyposis (Gardner's syndrome). The most striking observation was, however, that up to 80% of the affected patients (compared with less than 5% in the normal control population, P less than 0.05) had multiple minor bone anomalies demonstrable by x-ray screening of the mandible, chest, and long bones. We suggest that a generalized (inherited or mutant) defect in growth regulation of connective tissue is the most important underlying cause for the DT. However, the other factors, including hormonal effects, trauma, and pregnancy contribute to the growth behavior of the tumor.

The desmoid tumor. III. A biochemical and genetic analysis.

We have carefully examined four patients with desmoid tumor (DT) and their 31 relatives. In three of four cases, biopsies of the DT demonstrated low yet significant amounts of estrogen but not progesterone receptors in the tumor cytosol. In the fourth case, where the receptors were not demonstrable, the affected patient was a menopausal woman and the receptors may have been blocked by endogenous estrogen. Fourteen of their 31 relatives demonstrated multiple minor bone malformations in x-ray screening of the skeleton. The inheritance of these malformations was compatible with an autosomal dominant trait with variable penetrance. These findings are compatible with our suggestion that the basic underlying cause for DT is an inherited defect in growth regulation of the connective tissue. When a trauma is superimposed on such an individual, a DT may result. The growth of the tumor is, however, controlled primarily by sex hormones, estrogen predominance over progesterone being inducive to tumor growth.

Effect of age on muscle hypertrophy induced by resistance training.

BACKGROUND: Previous research has shown that resistance training induces muscle hypertrophy in older subjects, but has not clarified whether the degree of hypertrophy is affected by age. The present study was done to test the hypothesis that men and women over 60 years old have a smaller hypertrophic response to resistance training than young adults. METHODS: Cross-sectional areas (CSA) of muscle in the thigh and upper arm were determined before and after 3 months of progressive resistance training by magnetic resonance imaging (MRI) in 9 young (22-31 yr, 5 male and 4 female) and 8 old (62-72 yr, 4 male and 4 female) subjects. Strength was determined by 3-repetition-maximum (3RM) testing. The amount of weight lifted during the training program was proportional to baseline strength. RESULTS: Mean pretraining 3RM strength, per cm2 CSA, was less in the older group for all muscle groups examined (16 +/- 6% for elbow flexors, p < .02; 40 +/- 7% for knee flexors, p < .001; 19 +/- 9% for knee extensors, p < .05). Mean training-induced increases in muscle CSA were less in the older group for elbow flexors (22 +/- 4% in young, 9 +/- 4% in old, p < .05) and knee flexors (8 +/- 2% in young, 1 +/- 2% in old, p < .01), but not for knee extensors (4 +/- 1% in young, 6 +/- 2% in old). Mean training-induced increases in specific tension (ratio of 3RM strength to CSA) were similar in young and old groups for elbow flexors (21 +/- 5% in young, 19 +/- 5% in old) and knee extensors (38 +/- 6% in young, 32 +/- 14% in old), but were greater in the older group for knee flexors (28 +/- 5% in young, 64 +/- 13% in old, p < .02). CONCLUSIONS: Aging can attenuate the hypertrophic response of muscle groups to resistance training, when the training load is proportional to baseline strength. However, aging does not impair training-induced increases in specific tension.

Fat-suppression MR imaging of the orbit.

The effect of fat suppression on orbital MR imaging was tested by using a derivative of the Dixon method called chopper fat suppression in eight normal volunteers and eight patients with normal conventional orbital MR studies. Chopper fat suppression requires no postacquisition image processing or increased scan time and can be applied through a wide range of T1 to T2 weighting. In normal orbits, fat suppression was found to be advantageous for imaging the lacrimal gland and the optic nerve. Using fat-suppressed T1- or intermediate-weighted sequences, 2000/30 (TR/TE), the optic nerve was recognized by its high signal intensity relative to adjacent CSF, dural sheath, and surrounding fat. The technique minimized loss of anatomic detail by reducing chemical shift misregistration artifact. Disadvantages included an overall lower orbital signal/noise ratio. When used in conjunction with a TR/TE combination carefully selected for both anatomic region of interest and suspected pathology, the fat-suppression technique has the potential for improving the visualization of orbital lesions.

A comparison of default and reduced bandwidth MR imaging of the spine at 1.5 T.

The value of a reduced bandwidth MR imaging technique was tested prospectively in 51 spinal MR examinations by using default (16 kHz) bandwidth, 2000/30, 90 (TR/TEs) and 600/30, and reduced (8 kHz) bandwidth, 2000/48, 92 and 600/30, techniques at 1.5 T. Bandwidth reduction was used to maintain the signal-to-noise ratio for a reduced scan time. Concerns have been raised as to the effect of bandwidth reduction at high field, since a savings in time or an increased signal-to-noise ratio occur at the expense of increased chemical shift misregistration artifact. However, when appreciable, the chemical shift-related artifact in the spine was typically located in the frequency-encoding direction at the vertebral body/disk space interface or the dural sac/epidural fat interface in the lower lumbosacral region and was easily distinguished from pathologic lesions. There were no missed diagnoses with the reduced bandwidth technique. This study suggests that chemical shift-related artifact will rarely be confused with pathology by an experienced reader and suggests a clinical role for the bandwidth technique to decrease scanning time in uncooperative patients or to allow acquisition of additional imaging planes in a reasonable time.

Three-dimensional registration and fusion of ultrasound and MRI using major vessels as fiducial markers.

This paper describes fusion of three-dimensional (3-D) ultrasound (US) and magnetic resonance imaging (MRI) data sets, without the assistance of external fiducial markers or external position sensors. Fusion of these two modalities combines real-time 3-D ultrasound scans of soft tissue with the larger anatomical framework from MRI. The complementary information available from multiple imaging modalities warrants the development of robust fusion capabilities. We describe the data acquisition, specialized algorithms, and results for 3-D fused data from phantom studies and in vivo studies of the normal human vasculature and musculoskeletal systems.

Prevention of venous thrombosis after total knee arthroplasty. Comparison of antithrombin III and low-dose heparin with dextran.

In a prospective, randomized trial, we compared the efficacy of a combination of antithrombin III and heparin with that of dextran 40 as prophylaxis against venous thrombosis after total knee arthroplasty. Ascending venography identified thrombosis in about one-third of the patients who received the combination of antithrombin III and heparin, compared with about four-fifths of those who received dextran (p less than 0.001). In both groups, the patients who had venous thrombosis had a significantly lower concentration of antithrombin III postoperatively than those who did not have thrombosis. Venous thrombosis occurred in all patients in whom the concentration of antithrombin III was less than 65 per cent postoperatively. These findings demonstrated that, after total knee replacement, the combination of antithrombin III and heparin effectively reduces the incidence of postoperative venous thrombosis and is significantly better than dextran. Furthermore, the findings suggested a relationship between postoperative deficiency of antithrombin III and the occurrence of thrombotic complications.