Evaluation of vertebral fracture assessment by dual X-ray absorptiometry in a multicenter setting.

SUMMARY: The utility of vertebral fracture assessment (VFA) by DXA to detect prevalent vertebral fracture in a multicenter setting was investigated by comparison to conventional radiography. While limited by lower image quality, overall performance of VFA was good but had a tendency to miss mild prevalent fractures. INTRODUCTION: In osteoporosis clinical trials standardized spine radiographs are used to detect vertebral fractures as a study endpoint. Lateral spine imaging with dual X-ray absorptiometry (DXA) scanners, known as vertebral fracture assessment (VFA) by DXA, presents a potential alternative to conventional radiography with lower radiation dose and greater patient convenience. METHODS: We investigated in a multicenter setting the ability of VFA to detect fractures in comparison with conventional radiography. The study examined 203 postmenopausal women who had imaging of the spine by DXA and radiography. Three radiologists experienced in vertebral fracture assessment independently read the VFA scans and radiographs using the Genant semiquantitative method on two occasions. CONCLUSIONS: Analyzing the data from all readable vertebrae, the kappa statistic, sensitivity, and specificity ranged from 0.64-0.77, 0.65-0.84, and 0.97-0.98, respectively. Considering only moderate and severe fractures improved the kappa statistic (0.80-0.91) and sensitivity (0.70-0.86). While image quality of VFA is inferior to radiography, the detection of vertebral fractures using visual scoring is feasible. However, VFA underperformed due to unreadable vertebrae and reduced sensitivity for mild fractures. Nevertheless, VFA correctly identified most moderate and severe vertebral fractures. Despite this limitation, VFA by DXA provides an important tool for clinical research.

In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius.

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (microFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n = 22, mean age 58 +/- 7 years) and (II) postmenopausal women with spine or femur BMD -1 SD to -2.5 SD below young normal (n = 37, mean age 62 +/- 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young's moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with microFE modeling in vivo in the study of osteoporosis.

An interactive tutorial-based training technique for vertebral morphometry.

The purpose of this work was to develop a computer-based procedure for training technologists in vertebral morphometry. The utility of the resulting interactive, tutorial based training method was evaluated in this study. The training program was composed of four steps: (1) review of an online tutorial, (2) review of analyzed spine images, (3) practice in fiducial point placement and (4) testing. During testing, vertebral heights were measured from digital, lateral spine images containing osteoporotic fractures. Inter-observer measurement precision was compared between research technicians, and between technologists and radiologist. The technologists participating in this study had no prior experience in vertebral morphometry. Following completion of the online training program, good inter-observer measurement precision was seen between technologists, showing mean coefficients of variation of 2.33% for anterior, 2.87% for central and 2.65% for posterior vertebral heights. Comparisons between the technicians and radiologist ranged from 2.19% to 3.18%. Slightly better precision values were seen with height measurements compared with height ratios, and with unfractured compared with fractured vertebral bodies. The findings of this study indicate that self-directed, tutorial-based training for spine image analyses is effective, resulting in good inter-observer measurement precision. The interactive tutorial-based approach provides standardized training methods and assures consistency of instructional technique over time.

Characterization of atherosclerotic plaques at the carotid bifurcation: correlation of high-resolution MR imaging with histologic analysis--preliminary study.

The clinical symptoms and morbidity that result from carotid artery disease, the primary cause of stroke, are mainly due to plaque ulceration, thrombosis, intraplaque hemorrhage, and thinned fibrous caps. The contents of atherosclerotic plaques of the carotid artery can be determined with in vivo high-resolution magnetic resonance imaging with flow suppression. Eight patients scheduled to undergo endarterectomy and four healthy volunteers were imaged with a 1.5-T imager and custom-made carotid phased-array coils. T1-weighted spin-echo images and cardiac-gated proton-density--weighted fast spin-echo images were acquired. In vivo imaging findings as determined by three radiologists were correlated with ex vivo imaging and histologic findings. Among the eight plaque specimens, regions of hemorrhage, calcium, lipid deposits, and fibrous plaques were identified on T1- and proton-density-weighted images. Calcium and lipid deposits were detectable on both T1- and proton-density--weighted images. Hemorrhage and fibrous plaques were better demonstrated on proton-density--weighted images.

Intestinal absorption of Mn-mesoporphyrin in a small bowel sac system: effect of oleic acid.

RATIONALE AND OBJECTIVES: The authors investigated the effect of oleic acid (cis-9-octadecenoic acid) (OA), a lipidic carrier, on the intestinal absorption rate and T1 relaxation time of manganese (III) mesoporphyrin (Mn-mesoporphyrin), a prototype hepatobiliary contrast agent for magnetic resonance imaging. METHODS: Mn-mesoporphyrin was formulated with OA at various concentrations. Small bowel sacs were created in 36 rats and filled with complexed and free Mn-mesoporphyrin. Intestinal absorption of Mn-mesoporphyrin was measured with spectrophotometry at 364 nm. T1 relaxation times were measured in samples of Mn-mesoporphyrin solutions, bowel wall, liver, and bile. RESULTS: Absorption rates ranged from 4.2%/cm2/h to 13%/cm2/h. Absorption was greatest (13%/cm2/h) when a combination of 1 mmol/L Mn-mesoporphyrin and 26.5 mmol/L OA was used. The T1 of bile decreased from 2,480 to 248 msec (maximum decrease) in rats that received Mn-mesoporphyrin. CONCLUSION: Mn-mesoporphyrin is absorbed from the small bowel in both the lipid-associated and free form, resulting in substantial shortening of the T1 in bile.

Randomized clinical trial comparing mitoxantrone with epirubicin and with doxorubicin, each combined with cyclophosphamide in the first-line treatment of patients with metastatic breast cancer.

Two hundred and twenty-four patients with advanced breast cancer were enrolled in a multicenter prospective randomized clinical study and received either doxorubicin (40 mg/m2), or epirubicin (40 mg/m2) or mitoxantrone (12 mg/m2) each combined with cyclophosphamide (600 mg/m2) i.v. In the patient collective the following response rates were observed: complete response 12.1%; partial response 30.6%; stable disease 40.5%; progressive disease 16.8%. A complete response was observed significantly less often in patients where more than one organ site was involved as compared to those patients with only one metastatic site. The mean time period required to reach a best response was 3.7 months. There was no significant difference between the response rates in the three arms. In comparing the observed toxicities in 1,434 treatment cycles, there was a significant difference with regard to leukocytopenia (mitoxantrone arm exhibiting more than either epirubicin and doxorubicin) although infections did not occur more frequently in the mitoxantrone arm; with regard to alopecia, mitoxantrone and epirubicin arms both exhibited less than doxorubicin. It is noteworthy that no patient who had previously received adjuvant chemotherapy achieved a complete response (p = 0.006). The overall significance of these findings can only be clearly evaluated when survival times can be measured.

Serum neopterin levels in lung and breast cancer patients undergoing radiotherapy and/or chemotherapy.

The elevated neopterin levels observed in numerous haemotological diseases and parenchymatous malignomas suggested neopterin might be useful as a tumor marker. In a group of 60 patients suffering from advanced lung (18) or breast (42) cancer, serial determinations of serum neopterin were made before, during and after radiation and/or chemotherapy, during an observation period of 18 months, to check the potential value of neopterin in the therapeutic management of these tumor types. The neopterin profiles were compared with the clinical course and analysed with regard to response to therapy. Numbers of pathologically elevated serum neopterin levels were low. In only few cases was any agreement detected between changes in neopterin levels and therapeutic effects. Even chemotherapeutically induced depression in white blood counts generally did not increase serum neopterin levels. Thus the clinical suitability of neopterin as an adjuvant parameter in assessing therapeutic effects in lung or breast cancer could not be documented.