Osteoarthritis of the knee: association between clinical features and MR imaging findings.

PURPOSE: To prospectively evaluate the association between clinical features and structural abnormalities found at magnetic resonance (MR) imaging in patients with osteoarthritis (OA) of the knee. MATERIALS AND METHODS: The study was approved by the institutional medical ethics review board. Written informed consent was obtained from each patient. MR images of the knee were obtained from 205 (42 [20%] men, 163 [80%] women; median age, 60 years; range, 43-77 years) patients in whom symptomatic OA at multiple joint sites was diagnosed. MR images were analyzed for various abnormalities of OA. All patients were interviewed concerning pain and stiffness in the knee that was imaged. Odds ratios (ORs) with 99% confidence intervals (CIs) were used to determine the association between the imaging findings and clinical features of OA. RESULTS: A large joint effusion was associated with pain (OR, 9.99; 99% CI: 1.28, 149) and stiffness (OR, 4.67; 99% CI: 1.26, 26.1). The presence of an osteophyte in the patellofemoral compartment (OR, 2.25; 99% CI: 1.06, 4.77) was associated with pain. All other imaging findings, including focal or diffuse cartilaginous abnormalities, subchondral cysts, bone marrow edema, subluxation of the meniscus, meniscal tears, or Baker cysts, were not associated with symptoms. CONCLUSION: Findings of this study indicate that only two associations exist between clinical symptoms and structural findings found on MR images in patients with OA of the knee.

Magnetic resonance characterization of tumor microvessels in experimental breast tumors using a slow clearance blood pool contrast agent (carboxymethyldextran-A2-Gd-DOTA) with histopathological correlation.

Carboxymethyldextran (CMD)-A2-Gd-DOTA, a slow clearance blood pool contrast agent with a molecular weight of 52.1 kDa, designed to have intravascular residence for more than 1 h, was evaluated for its potential to characterize and differentiate the microvessels of malignant and benign breast tumors. Precontrast single-slice inversion-recovery snapshot FLASH and dynamic contrast-enhanced MRI using an axial T1-weighted three-dimensional spoiled gradient recalled sequence was performed in 30 Sprague-Dawley rats with chemically induced breast tumors. Endothelial transfer coefficient and fractional plasma volume of the breast tumors were estimated from MRI data acquired with CMD-A2-Gd-DOTA enhancement injected at a dose of 0.1 mmol Gd/kg body weight using a two-compartment bidirectional model of the tumor tissue. The correlation between MRI microvessel characteristics and histopathological tumor grade was determined using the Scarff-Bloom-Richardson method. Using CMD-A2-Gd-DOTA, no significant correlations were found between the MR-estimated endothelial transfer coefficient or plasma volumes with histological tumor grade. Analysis of CMD-A2-Gd-DOTA-enhanced MR kinetic data failed to demonstrate feasibility for the differentiation of benign from malignant tumors or for image-based tumor grading.

The choice of region of interest measures in contrast-enhanced magnetic resonance image characterization of experimental breast tumors.

OBJECTIVES: The objectives of this study were to determine if magnetic resonance (MR) estimates of quantitative tissue microvascular characteristics from regions of interest (ROI) limited to the tumor periphery provided a better correlation with tumor histologic grade than ROI defined for the whole tumor in cross-section. METHODS: A metaanalysis was based on 98 quantitative MR image breast tumor characterizations acquired in 3 separate experimental studies using identical methods for tumor induction and contrast enhancement. RESULTS: The endothelial transfer coefficient (K) of albumin (Gd-DTPA)30 from the tumor periphery correlated (r = 0.784) significantly more strongly (P < 0.001) with the pathologic tumor grade than K derived from the whole tumor (r = 0.604). K estimates, either from the tumor periphery or from the whole tumor, correlated significantly more strongly with histologic grade (P < 0.01) than MR image estimates of fractional plasma volume (fPV) from either tumor periphery (r = 0.368) or whole tumor (r = 0.323). CONCLUSIONS: K estimates from the tumor periphery were the best of these measurable MR image microvascular characteristics for predicting the histologic grade.

MRI assessment of knee osteoarthritis: Knee Osteoarthritis Scoring System (KOSS)--inter-observer and intra-observer reproducibility of a compartment-based scoring system.

OBJECTIVE: To develop a scoring system for quantifying osteoarthritic changes of the knee as identified by magnetic resonance (MR) imaging, and to determine its inter- and intra-observer reproducibility, in order to monitor medical therapy in research studies. DESIGN AND PATIENTS: Two independent observers evaluated 25 consecutive MR examinations of the knee in patients with previously defined clinical symptoms and radiological signs of osteoarthritis. We acquired on a 1.5 T system: coronal and sagittal proton density- and T2-weighted dual spin echo (SE) images, sagittal three-dimensional T1-weighted gradient echo (GE) images with fat suppression, and axial dual turbo SE images with fat suppression. Images were scored for the presence of cartilaginous lesions, osteophytes, subchondral cysts, bone marrow edema, and for meniscal abnormalities. Presence and size of effusion, synovitis and Baker's cyst were recorded. All parameters were ranked on a previously defined, semiquantitative scale, reflecting increasing severity of findings. Kappa, weighted kappa and intraclass correlation coefficient (ICC) were used to determine inter- and intra-observer variability. RESULTS: Inter-observer reproducibility was good (ICC value 0.77). Inter- and intra-observer reproducibility for individual parameters was good to very good (inter-observer ICC value 0.63-0.91; intra-observer ICC value 0.76-0.96). CONCLUSION: The presented comprehensive MR scoring system for osteoarthritic changes of the knee has a good to very good inter-observer and intra-observer reproducibility. Thus the score form with its definitions can be used for standardized assessment of osteoarthritic changes to monitor medical therapy in research studies.

Noncontrast dynamic magnetic resonance imaging for quantitative assessment of female sexual arousal.

PURPOSE: We evaluated a noncontrast, dynamic magnetic resonance imaging (MRI) technique for quantitative evaluation of the female sexual arousal response and compared these results with those of a previously described, contrast enhanced MRI technique. MATERIALS AND METHODS: Eight normal, healthy volunteer women underwent 2 separate MRI sessions, during which they were shown audiovisual material consisting of interleaved neutral and audiovisual sexual stimulation segments. Serial high resolution MRI of the genital structures was done at 3-minute intervals during a 45-minute period. Images were analyzed in blinded fashion and measurements of clitoral volume with time were obtained for each subject. Measured clitoral volumes together with the percent change in clitoral volume during audiovisual sexual stimulation for MRI sessions 1 and 2 were compared within subjects. Results were also compared to those of prior contrast enhanced MRI studies in the same subjects. RESULTS: There was excellent intrasubject reproducibility between sessions 1 and 2 using the noncontrast MRI technique (r = 0.99). There was also excellent agreement between the current noncontrast study and prior contrast enhanced studies with a correlation coefficient of 0.89. CONCLUSIONS: Dynamic, noncontrast MRI of the female genitalia appears to be a reproducible, nonintrusive and objective way to assess quantitatively the sexual arousal response in women without sexual difficulties.

Serial MR imaging with MS-325 for evaluating female sexual arousal response: determination of intrasubject reproducibility.

PURPOSE: To determine if a similar sexual arousal response in normal, healthy women could be obtained and monitored by serial magnetic resonance (MR) imaging at two separate sessions. MATERIALS AND METHODS: Serial imaging of the external genitalia was performed on nine healthy, sexually functional women at two separate MR sessions after administration of the contrast agent, MS-325. Images were obtained every three minutes during a 45-minute study period during each MR session. The second MR session began approximately 45 minutes after the end of the first MR session. While undergoing imaging, subjects viewed videotapes that contained neutral and sexually-explicit material through an audiovisual system. Analysis performed at each time point consisted of visual evaluation of the images, clitoral and femoral vein signal intensity measurements, relative regional blood volume calculations, and clitoral volume measurements. Statistical analysis of the results consisted of calculating correlation coefficients of the two MR sessions by using the least square fit method. RESULTS: All nine subjects reported sexual arousal on subjective questionnaires at each MR session. Post-contrast MS-325 MR images showed strong enhancement of the external genitalia at each session. There was excellent correlation between the two sessions for the clitoral volume measurements of all nine subjects. The correlation coefficient, r(2), was 0.95. CONCLUSION: The sexual arousal response in normal, healthy women can be monitored by serial imaging combined with the use of the contrast agent, MS-325, and similar results can be reproduced at two different MR sessions. This method holds promise for future studies of women with female sexual arousal dysfunction.

MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer model.

The aim of this study was to evaluate the potential of dynamic magnetic resonance imaging (MRI) enhanced by macromolecular contrast agents to monitor noninvasively the therapeutic effect of an anti-angiogenesis VEGF receptor kinase inhibitor in an experimental cancer model. MDA-MB-435, a poorly differentiated human breast cancer cell line, was implanted into the mammary fat pad in 20 female homozygous athymic rats. Animals were assigned randomly to a control (n=10) or drug treatment group (n=10). Baseline dynamic MRI was performed on sequential days using albumin-(GdDTPA)30 (6.0 nm diameter) and ultrasmall superparamagnetic iron oxide (USPIO) particles (approximately 30 nm diameter). Subjects were treated either with PTK787/ZK 222584, a VEGF receptor tyrosine kinase inhibitor, or saline given orally twice daily for 1 week followed by repeat MRI examinations serially using each contrast agent. Employing a unidirectional kinetic model comprising the plasma and interstitial water compartments, tumor microvessel characteristics including fractional plasma volume and transendothelial permeability (K(PS)) were estimated for each contrast medium. Tumor growth and the microvascular density, a histologic surrogate of angiogenesis, were also measured. Control tumors significantly increased (P<0.05) in size and in microvascular permeability (K(PS)) based on MRI assays using both macromolecular contrast media. In contrast, tumor growth was significantly reduced (P<0.05) in rats treated with PTK787/ZK 222584 and K(PS) values declined slightly. Estimated values for the fractional plasma volume did not differ significantly between treatment groups or contrast agents. Microvascular density counts correlated fairly with the tumor growth rate (r=0.64) and were statistically significant higher (P<0.05) in the control than in the drug-treated group. MRI measurements of tumor microvascular response, particularly transendothelial permeability (K(PS)), using either of two macromolecular contrast media, were able to detect effects of treatment with a VEGF receptor tyrosine kinase inhibitor on tumor vascular permeability. In a clinical setting such quantitative MRI measurements could be used to monitor tumor anti-angiogenesis therapy.

Dynamic MR imaging of the sexual arousal response in women.

The purpose of our studies was to evaluate whether MR imaging could be used to noninvasively observe and measure the sexual arousal response in normal women. We tested the feasibility as well as the reproducibility of rapid, dynamic, serial high-resolution MR imaging of the genital structures during presentation of neutral and sexually stimulating video material. Results show that these MRI techniques can visualize significant changes in clitoral volume during the stimulus segment of the video presentation. Quantitative measurements made of these changes were robust and reproducible. These studies suggest that MRI techniques may be a useful tool to improve our understanding of the physiology involved with the sexual arousal response in women. These MRI techniques may also prove useful as a surrogate end point marker for testing efficacy of future new treatments for women with sexual arousal disorder.

Female genitalia: dynamic MR imaging with use of MS-325 initial experiences evaluating female sexual response.

PURPOSE: To determine whether magnetic resonance (MR) imaging with MS-325, a recently developed blood pool contrast agent, can depict sexual arousal response in healthy women. MATERIALS AND METHODS: Serial MR imaging of the external genitalia was performed in 12 healthy sexually functional women before and after administration of MS-325. MR images were obtained every 3 minutes during a 45-minute examination. During the examination, the subjects viewed neutral and erotic video material while they were in the magnet bore. MR image analysis at each interval consisted of vaginal wall, vaginal mucosa, and clitoris assessments; femoral vein signal intensity measurements; relative regional blood volume (rRBV) calculations; and clitoral volume measurements. Statistical analysis of the results was performed with a t test. RESULTS: On subjective questionnaires, all subjects in the test group reported being sexually aroused. MS-325-enhanced MR images showed strong contrast enhancement of the external genitalia. The rRBV in the glans clitoris of seven of 10 subjects and in the clitoral body of eight of these subjects increased significantly (P <.05) during erotic visual stimulation. All 10 subjects had a significant (P <.05) increase in clitoral size. There were no significant differences in any measures between the pre- and postmenopausal study groups. CONCLUSION: The sexual arousal response in healthy women can be monitored at serial MR imaging with MS-325. This examination holds promise for future studies of sexual arousal dysfunction in women.