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Assessment of progression in knee osteoarthritis: results of a 1 year study comparing arthroscopy and MRI.

OBJECTIVE: The objectives of this study were to determine the sensitivity to change of magnetic resonance imaging (MRI) quantification of chondropathy after 1 year in osteoarthritis of the medial tibiofemoral compartment and to assess the predictive value of subchondral bone marrow edema and bone abnormalities on progression of chondropathy. DESIGN: Twenty patients with symptomatic knee osteoarthritis of the medial compartment underwent a prospective, longitudinal study. All patients were evaluated the same day at entry and after 1 year by plain weight-bearing radiographs, MRI with a three-dimensional gradient-echo sequence, using a 0.2-T dedicated MR unit, and arthroscopy. The medial tibiofemoral chondropathy was quantified blindly with MRI and arthroscopy using the French Society of Arthroscopy (SFA) score. Presence of subchondral bone marrow edema and bone abnormalities on initial MRI was recorded in order to evaluate their influence on both unchanged and worsened chondropathy after 1 year. RESULTS: After 1 year, no statistically significant changes were observed with plain radiographs and arthroscopy. At variance, a statistically significant worsening of chondropathy was found with MRI using the SFA-MR score (P=0.01). SFA-MR score was the most responsive outcome. Absence of subchondral bone abnormalities and bone marrow edema on initial MR assessment predicted absence of worsening of chondropathy after 1 year. CONCLUSION: MRI appears promising for evaluating progression of knee osteoarthritis.

Adult↗

Quantification of the 3D relative movement of external marker sets vs. bones based on magnetic resonance imaging.

BACKGROUND: Most in vivo knee kinematic analyses are based on external markers attached to the shank and the thigh. Literature data show that markers positioning and soft tissues artifacts affect the kinematic parameters of the bones true movement. Most of the techniques of quantification used were invasive. The aim of the present study was to develop and apply a non-invasive methodology to compute the relative movement between the bones and the markers. METHODS: Magnetic resonance imaging acquisitions were performed on the right knee of eleven volunteers without knee injury. The subjects were equipped with external magnetic resonance imaging-compatible marker sets. A foot drive device allowed the subjects to perform an actively loaded knee extension. The whole volume of the subject's knee was processed for four sequentially held knee flexion positions during the knee movement. The bones and external marker sets geometry were reconstructed from magnetic resonance imaging images. Then a registration algorithm was applied to the bones and the relative movement of the thigh and shank marker sets with respect to their underlying bones was computed. FINDINGS: The protocol resulted in a good geometrical accuracy and reproducibility. Marker sets movement differ from that of the bones with a maximum of 22 mm in translation and 15 degrees in rotation and it affects the knee kinematics. INTERPRETATION: Marker sets relative movement modify the knee movement finite helical axes direction (range 10-35 degrees ) and localization (range 0-40 mm). The methodology developed can evaluate external marker set system to be used for kinematic analysis in a clinical environment.

Adult↗

Quantification and validation of predictive values of occlusal variables in temporomandibular disorders using a multifactorial analysis.

STATEMENT OF PROBLEM: A consensus is lacking on the association between occlusal variables and temporomandibular disorders (TMDs). PURPOSE: This study estimated the maximum potential power of occlusal variables to differentiate patients with TMD from asymptomatic normal adult subjects. MATERIAL AND METHODS: The occlusal characteristics in 2 sets of female patients with intracapsular TMD (1993, n = 257, and 1998, n = 124) differentiated into disk displacement and osteoarthrosis subdiagnoses were compared with asymptomatic female controls (n = 51 and 47) with multiple logistic regression analysis. Significant variables and total contribution to the log likelihood were compared with the predictive value of univariate analysis, including sensitivity and specificity. RESULTS: Occlusal factors in the females (1993, 1998) explained no more than 4.8% to 27.1% of the log likelihood. In comparison to the logistic regression analysis, univariate analysis was less predictive of patients with TMD, due to notably lower sensitivity. Patients with disk displacement were mainly characterized by unilateral posterior crossbite and longer RCP-ICP slides. Patients with osteoarthrosis were most consistently characterized by longer RCP-ICP slides and larger overjet, and in part to reduced overbite. Significant relative risk for disease (odds ratio > 2:1) was mainly associated with infrequent, more extreme ranges of occlusion measurements. CONCLUSION: Occlusal factors may be cofactors in the identification of patients with TMD, but their role should not be overstated. Some occlusal variation may be a consequence of rather than a cause for TMD. Single variables have more limited value and it takes sets of adverse variables to model TMD. Combinations of variables appear to be disease specific. Some extreme ranges of occlusion were the domain of patients with TMD, but most patients were within the normal ranges.

Adult↗

Increase in Purkinje cell gain associated with naturally activated climbing fiber input.

These experiments were designed to test the hypothesis that climbing fiber inputs evoked by a peripheral stimulus increase the responsiveness of Purkinje cells to mossy fiber inputs. This hypothesis was based on a previous series of observations demonstrating that spontaneous climbing fiber inputs are associated with an accentuation of the Purkinje cell responses to subsequent mossy fiber inputs (10, 12). Furthermore, short-term nonpersistent interactions between climbing and mossy fiber inputs have been an important aspect of many theories of cerebellar function (5, 7, 8, 12, 36). Extracellular unitary recordings were made from Purkinje cells in lobule V of decerebrate, unanesthetized cats. To activate mossy and climbing fiber inputs, the forepaw was passively flexed by a Ling vibrator system. A data analysis was developed to sort the simple spike trials into two groups, based on the presence or absence of complex spikes activated by the stimulus. In addition, during those trials in which complex spikes were activated, the simple spike train was aligned on the occurrence of the complex spike. For each simple spike response to the forepaw input, the average firing rate during the response was compared to background both in those trials in which complex spikes were activated and in those in which they were not. The ratio of the response amplitudes in the histograms constructed from these two groups of trials permitted a quantification of the change in responsiveness when climbing fiber inputs were activated. The results show that both excitatory and inhibitory simple spike responses are accentuated when associated with the activation of a complex spike. Using an arbitrary level of a gain change ratio of 120% as indicating a significant modification, 64% of the response components analyzed increased their amplitude when climbing fiber input was present. Simple spike response components occurring prior to complex spike activation were usually not accentuated, although in a few cells the amplitude of this component of the response increased. In addition, in a small number of cells the occurrence of complex spikes was associated with a new simple spike component. For excitatory responses, the magnitude of the gain change ratio was shown to be inversely related to the amplitude of the simple spike response evoked by the mossy fiber inputs. The data obtained is consistent with the hypothesis that the climbing fiber input is associated with an increase in the responsiveness of Purkinje cells to mossy fiber inputs. The increased responsiveness occurs whether the simple spike modulation evoked by the peripheral stimulus is excitatory or inhibitory. The change in responsiveness is short term and nonpersistent. It is argued that the activation of climbing fiber inputs to the cerebellar cortex is associated with an increase in the gain of Purkinje cells to mossy fiber inputs activated by natural peripheral stimuli.

Afferent Pathways↗

Quantification of full-range-of-motion unilateral and bilateral knee flexion and extension torque ratios.

OBJECTIVES: To evaluate the reliability and variability of repeated measurements of isometric knee flexion and extension strength, to quantify the extent of measurement error that may occur due to gravity, and to quantify isometric knee flexion/extension torque ratios at multiple angles through a full range of motion. DESIGN: Reliability assessment. SETTING: A university exercise center. PARTICIPANTS: Seventy-seven healthy men and women recruited from a university and surrounding community. INTERVENTION: Isometric knee flexion and extension strength tests. MAIN OUTCOME MEASURES: Knee flexion/extension strength was measured at 6 degrees, 24 degrees, 42 degrees, 60 degrees, 78 degrees, 96 degrees, and 108 of knee flexion. Before each contraction, subjects were instructed to completely relax the limbs to measure the mass of the lower leg. Torque values obtained during relaxation at each angle were added to or subtracted from "Total Torque" (TTQ) at peak exertion. The adjusted value was recorded as "Net Muscular Torque" (NMT). RESULTS: Reliability for the unilateral and bilateral tests was high (r =.88 to r=.98) and measurement variability low (SEM%=5.1% to 12.6%). There was a statistically significant difference at each angle of measurement between the TTQ and NMT values for both knee flexion and extension. Knee flexion/extension ratios were highly dependent on the angle tested, ranging from 1.30 (at 60) to .31 (at 1080). CONCLUSIONS: Isometric testing, using standardized angles, can reliably quantify knee flexion/extension strength. Furthermore, these findings emphasize the importance of correcting for the mass of the lower leg when assessing muscle function. Angle-specific knee flexion/extension torque ratios should provide clinicians with a more precise method of evaluating muscular balance (imbalance) throughout the range of motion.

Adolescent↗

A preliminary protocol for multi-professional centers for the determination of signs and symptoms of temporomandibular disorders.

The objective of the present study was to test a protocol for the quantification of the frequency and severity of signs and symptoms of temporomandibular disorders (TMD) according to patient perception during two phases of investigation. The protocol was developed based on the signs and symptoms most frequently reported in the literature and on the circumstances in which they produce discomfort. Eighty-four patients diagnosed with TMD by functional examination of the masticatory system responded to the protocol questions and indicated the severity of signs and symptoms using an eleven point numerical scale (Phase 1). Forty-two patients were fitted with an occlusal splint (treated group) and the remaining participants did not use a splint (control group). The protocol questions were asked after 50 days of treatment (Phase 2). Based on the results of nonparametric statistical analysis, the incidence of signs and symptoms was high in Phase 1 and significant, with no difference between the groups, whereas the treated and control groups differed in Phase 2. A comparison between Phases 1 and 2 showed that only the treated group presented a reduction in the severity of signs and symptoms. The study showed that using this protocol, it is possible to define the frequency and severity of symptoms as well as the effect of the treatment. The advantage of this protocol is that it would complement the data obtained using clinical examination with information provided by the patient in a measurable manner.

Epidemiologic Methods↗

In vivo MR angiographic quantification of axial and twisting deformations of the superficial femoral artery resulting from maximum hip and knee flexion.

PURPOSE: The goal of this study was to quantify in vivo deformations of the superficial femoral artery (SFA) during maximum knee and hip flexion with use of magnetic resonance (MR) angiography to improve description of the complex, dynamic SFA environment. MATERIALS AND METHODS: Contrast medium-enhanced MR angiography was performed on the leg vasculature of eight healthy adults in the supine and fetal positions. The SFA was defined as the centerline path of the iliofemoral segment from the profunda femoris to the descending genicular artery. Deformations that resulted from flexion from the supine position to the fetal position were quantified with the SFA path and its branches. RESULTS: Fourteen SFAs shortened from the supine position to fetal position, whereas two lengthened. Six of eight left SFAs twisted counterclockwise, and seven of eight right SFAs twisted clockwise. Straightness percentages for supine and fetal SFAs were 99.1%+/-0.4% and 98.7%+/-0.6%, respectively. From the supine position to the fetal position, the SFA shortened 13%+/-11% (P<.001) and twisted 60 degrees+/-34 degrees (P<.001). SFA arc length and percent shortening were strongly correlated (r>.8) between left and right limbs; however, no significant correlation existed for SFA twist angle. CONCLUSIONS: Complex and varying vascular and muscular anatomy among study participants made SFA lengths and deformations from the supine position to the fetal position unpredictable a priori; however, there were strong symmetries between left and right SFAs in terms of arc length, length change, and direction of twist. The data show that, from the supine position to the fetal position, the SFA tended to shorten and twist substantially, suggesting these as possible fracture mechanisms and also providing important parameters for stent design.

Adult↗

Width of the articular cartilage of the hip: quantification by using fat-suppression spin-echo MR imaging in cadavers.

OBJECTIVE: Use of MR imaging to measure the width of the articular cartilage has not been thoroughly investigated. The value of a selective fat-suppression spin-echo sequence in the quantitative assessment of articular cartilage of the hip was studied in cadavers. MATERIALS AND METHODS: Sagittal and coronal images were acquired in 10 cadaveric hips (age range at time of death, 62-81 years). On the coronal and sagittal MR images that were closest to the center of the femoral head, marks were placed every 30 degrees, with the midpoint of the femoral head used as a reference. Cartilage thickness was measured in 123 resulting locations. Sixty-three positions included both femoral and acetabular cartilages, and 60 positions included femoral cartilage without an acetabular counterpart. The findings were compared with corresponding anatomic sections. RESULTS: For the 60 locations containing only femoral cartilage, significant correlation between MR and anatomic sections was found (Pearson correlation coefficient = .34, p = .0089). Of the 63 locations containing both femoral and acetabular cartilages, the two cartilage layers could be differentiated on the MR images in 50 locations. In these 50, the MR and anatomic measurements of the femoral cartilage correlated significant (r = .58, p less than or equal to .0001). Measurements of the acetabular cartilage in these 50 locations yielded no significant correlation (r = .25, p = .08). When the entire cartilage (femoral plus acetabular) was measured in all 63 locations, the correlation between MR and anatomic measurements was .29 (p = .02). The correlation coefficients obtained in this investigation indicate considerable scattering of the data. CONCLUSION: Our results show that measurements of articular cartilage thickness of the hip on fat-suppression spin-echo MR images are not sufficiently accurate to be of clinical value.

Aged↗

The use of a force-controlled dynamic knee simulator to quantify the mechanical performance of total knee replacement designs during functional activity.

The experimental evaluation of any total knee replacement (TKR) design should include the pre-implantation quantification of its mechanical performance during tests that simulate the common activities of daily living. To date, few dynamic TKR simulation studies have been conducted before implantation. Once in vivo, the accurate and reproducible assessment of TKR design mechanics is exceedingly difficult, with the secondary variables of the patient and the surgical technique hindering research. The current study utilizes a 6-degree-of-freedom force-controlled knee simulator to quantify the effect of TKR design alone on TKR mechanics during a simulated walking cycle. Results show that all eight TKR designs tested elicited statistically different measures of tibial/femoral kinematics, simulated soft tissue loading, and implant geometric restraint loading during an identical simulated gait cycle, and that these differences were a direct result of TKR design alone. Maximum ranges of tibial kinematics over the eight designs tested were from 0.8mm anterior to 6.4mm posterior tibial displacement, and 14.1 degrees internal to 6.0 degrees external tibial rotation during the walking cycle. Soft tissue and implant reaction forces ranged from 106 and 222N anteriorly to 19 and 127N posteriorly, and from 1.6 and 1.8Nm internally to 3.5 and 5.9Nm externally, respectively. These measures provide valuable experimental insight into the effect of TKR design alone on simulated in vivo TKR kinematics, bone interface loading and soft tissue loading. Future studies utilizing this methodology should investigate the effect of experimentally controlled variations in surgical and patient factors on TKR performance during simulated dynamic activity.

Biomechanical Phenomena↗

Mast cell numbers in rheumatoid synovial tissues. Correlations with quantitative measures of lymphocytic infiltration and modulation by antiinflammatory therapy.

Synovial biopsy specimens from 20 patients with rheumatoid arthritis were subjected to quantitative analysis for several parameters of inflammation and for enumeration of synovial tissue mast cells. Strong positive correlations were found between numbers of mast cells per cubic millimeter of synovial tissue and the following synovial tissue parameters: inflammatory index (a quantification of lymphocytic infiltration), Leu-3a grade (T helper/inducer lymphocytes), Leu-1 grade (T lymphocyte), and plasma cell grade. A strong negative correlation was found between the synovial mast cell count and the extent of sublining layer fibrin deposition. Correlations between synovial mast cell count and Leu-2a grade, ratio of Leu-3a grade:Leu-2a grade, OKM1 grade, HLA-DR grade, and lining layer thickness grade did not reach statistical significance. In addition, we obtained synovial specimens from 6 of the patients both before and after long-term therapy with oral methotrexate and from 3 of the patients before, and 1 week after, an intraarticular injection of steroid. The 3 patients who had an intraarticular steroid injection showed a 67-96% decrease in the number of synovial tissue mast cells; there was no significant change in the number of synovial mast cells in the tissues of the 6 patients who received oral methotrexate. These observations are the first documentation of a quantitative relationship between the number of mast cells and the number and phenotypic profile of infiltrating lymphocytes in an inflamed tissue, which in this case, is human synovium. Our findings suggest that mast cells are involved in the pathologic interactions in rheumatoid arthritis and might play a role in the early phases of exacerbations of disease activity.

Administration, Oral↗

The changes in crosslink contents in tissues after formalin fixation.

The aim of this study was to detect crosslinks of collagen and elastin in formalin-fixed tissue, to perform quantification of these crosslinks, and to investigate the effects of formalin fixation on crosslink contents in human yellow ligament and cartilage. Pyridinoline (Pyr) is a stable and nonreducible crosslink of collagen. Pentosidine (Pen) is a senescent crosslink formed between arginine and lysine in matrix proteins, including collagen. Desmosine (Des) and its isomer isodesmosine (Isodes) are crosslinks specifically found in elastin. It is useful to measure crosslink contents of collagen and elastin as a way of investigating the properties of various tissues or their pathological changes. If it is possible to evaluate crosslinks of collagen and elastin in formalin-fixed tissues, we can investigate crosslinks in a wide variety of tissues. We used HPLC to compare the concentrations of Pyr, Pen, Des, and Isodes in the formalin-fixed tissues with their concentrations in the frozen tissues. Pyr and Pen were detected in both the formalin-fixed yellow ligament and the cartilage, and their concentrations were not significantly affected by or related to the duration of formalin fixation. Des and Isodes were detected in the formalin-fixed yellow ligament but in significantly lower amounts compared to the frozen samples. We concluded that crosslinks of collagen were preserved in formalin, but crosslinks of elastin were not preserved in it. The reason for this might be that formalin did not fix elastin tissues sufficiently or it destroyed, masked, or altered elastin crosslinks.

Aged↗

Quantification of the relative risk of multiple occlusal variables for muscle disorders of the stomatognathic system.

STATEMENT OF PROBLEM: There is no consensus on the association between occlusion and temporomandibular disorders (TMD). PURPOSE: The purpose of this study was to quantify the relative risk of multiple occlusal variables for muscle disorders of the stomatognathic system. MATERIAL AND METHODS: Eight occlusal features: retruded contact position (RCP) to maximum intercuspation (MI) slide length, vertical overlap, horizontal overlap, unilateral posterior reverse articulation, anterior open occlusal relationship, incisor dental midline discrepancy, mediotrusive interferences, and laterotrusive interferences, were clinically assessed by the same trained operator. The sample consisted of 81 women with a Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) axis I diagnosis of muscle disorder, for example myofascial pain, with or without limited opening, and 48 healthy women (control group). A stepwise multiple logistic regression was used to identify the significant associations between occlusal features and disease. RESULTS: A slide from the retruded contact position to maximum intercuspation > or =2 mm and mediotrusive interferences were the only 2 occlusal features significantly associated with the presence of myofascial pain according to the RDC/TMD criterion symptoms. The odds ratio for myofascial pain was 2.57 for a slide from RCP to MI > or =2 mm and 2.45 for mediotrusive interferences. The percentage of the total log likelihood for myofascial pain explained by the significant occlusal factors amounted to 10.8% (Nagelkerke's R2=0.108). The multifactorial model, including the 2 significant occlusal factors, showed an acuracy to predict disease of 66.7% (sensitivity 71.6%; specificity 58.3%). CONCLUSION: Occlusal features showed a low predictive value to detect muscle disorders of the stomatognathic system. Multifactorial complex pathologies, such as TMD, should be studied using multivariate statistical analyses, as univariate models may overestimate some resulting associations.

Adult↗

Inter-observer reliability of the arthroscopic quantification of chondropathy of the knee.

BACKGROUND: Several scoring systems have been proposed in order to quantify the degree of cartilage damage observed by arthroscopy of the knee in patients with osteoarthritis. OBJECTIVE: To evaluate the inter-observer reliability of five different scoring systems of arthroscopic evaluation for chondropathy in osteoarthritis of the knee and to evaluate the utility of a training session between different observations on these scoring systems. METHODS: Videotapes of knee arthroscopies on five patients with osteoarthritis demonstrating different levels of severity of cartilage damage of the medial tibiofemoral compartment were analyzed by nine observers prior to (pre-training evaluation) and 2 months after a 6 h training session (post-training evaluation) by the following scoring systems: (1) cartilage deterioration by a 100 mm visual analogue scale (VAS), (2) overall assessment of degeneration in the entire medial compartment (cartilage, meniscus, osteophyte) using a 100 mm VAS, (3) French Society of Arthroscopy (SFA) Scoring System, (4) SFA Grading System, (5) American College of Rheumatology (ACR) Scoring System. RESULTS: At the pre-training evaluation, the SFA grading system produced the highest coefficient of reliability (r = 0.94), the other systems recording levels of < or = 0.80. At the post-training evaluation, the coefficient of reliability was r > 0.80 for four of the five scoring systems, with lack of improvement in the ACR Scoring System. CONCLUSION: There was an improved and acceptable inter-observer reliability for at least 2 months follow-up in four of five evaluated scoring systems of arthroscopically graded osteoarthritis of the knee following a training session. A scoring system using a 100 mm VAS may produce the best inter-observer reliability. These results show that scoring chondropathy is possible and demonstrate the importance of training in the analysis of articular cartilage breakdown.

Arthroscopy↗

Quantitative detection of Borrelia burgdorferi by real-time PCR.

Currently, no easy and reliable methods allowing for the quantification of Borrelia burgdorferi in tissues of infected humans or animals are available. Due to the lack of suitable assays to detect B. burgdorferi CFU and the qualitative nature of the currently performed PCR assays, we decided to exploit the recently developed real-time PCR. This technology measures the release of fluorescent oligonucleotides during the PCR. Flagellin of B. burgdorferi was chosen as the target sequence. A linear quantitative detection range of 5 logs with a calculated detection limit of one to three spirochetes per assay reaction mixture was observed. The fact that no signals were obtained with closely related organisms such as Borrelia hermsii argues for a high specificity of this newly developed method. A similar method was developed to quantify mouse actin genomic sequences to allow for the standardization of spirochete load. The specificity and sensitivity of the B. burgdorferi and the actin real-time PCR were not altered when samples were spiked with mouse cells or spirochetes, respectively. To evaluate the applicability of the real-time PCR, we used the mouse model of Lyme disease. The fate of B. burgdorferi was monitored in different tissues from inbred mice and from mice treated with antibiotics. Susceptible C3H/HeJ mice had markedly higher burdens of bacterial DNA than resistant BALB/c mice, and penicillin G treatment significantly reduced the numbers of spirochetes. Since these results show a close correlation between clinical symptoms and bacterial burden of tissues, we are currently analyzing human biopsy specimens to evaluate the real-time PCR in a diagnostic setting.

Animals↗

Microscopic measurement of synovial membrane inflammation in rheumatoid arthritis: proposals for the evaluation of tissue samples by quantitative analysis.

Previous studies have used various techniques for microscopic analysis of rheumatoid synovium, ranging from rapid analysis of limited areas of tissue to detailed quantification of extensive areas. The sensitivity and reproducibility of these methods have not been tested. This study sought to determine the minimum area of rheumatoid synovium needed to allow accurate microscopic analysis of synovial inflammation. Multiple synovial tissue samples were obtained from patients with rheumatoid arthritis at knee arthroplasty (n = 10), knee arthroscopy (n = 10) and by blind needle biopsy (n = 23). Lining layer thickness, sublining T-cell infiltration and vascularity were measured in all high-power fields (hpf) throughout every sample obtained from each patient. These complete measured results were compared with estimated results from limited numbers of hpf from each patient. It was observed that lining layer thickness estimated from as few as five readings from 3 samples/patient correlated significantly with the measured results obtained from as many as 85 readings/patient [Tau (T) = 0.70-0.94 for the three groups, all P < or = 0.005). Estimated measures of T-cell infiltration and vascularity derived from only 17 randomly selected hpf from 3 samples/patient (equivalent to 1 mm2) correlated significantly with the measured results obtained from up to 150 hpf/patient (T = 0.65-0.94, all P < or = 0.002). Quantitative analysis of inflammation in synovial tissue samples is both accurate and practical when restricted to an evaluation of a limited number of microscopic fields. It is proposed that lining layer thickness may be confidently quantified from five randomly selected readings from three tissue samples, and that sublining T-cell infiltration and vascularity may be quantified from 17 randomly selected hpf from the same samples.

Antibodies, Monoclonal↗

Reliability of a quantification imaging system using magnetic resonance images to measure cartilage thickness and volume in human normal and osteoarthritic knees.

OBJECTIVE: The aim of this study was to evaluate the reliability of a software tool that assesses knee cartilage volumes using magnetic resonance (MR) images. The objectives were to assess measurement reliability by: (1) determining the differences between readings of the same image made by the same reader 2 weeks apart (test-retest reliability), (2) determining the differences between the readings of the same image made by different readers (between-reader agreement), and (3) determining the differences between the cartilage volume readings obtained from two MR images of the same knee image acquired a few hours apart (patient positioning reliability). METHODS: Forty-eight MR examinations of the knee from normal subjects, patients with different stages of symptomatic knee osteoarthritis (OA), and a subset of duplicate images were independently and blindly quantified by three readers using the imaging system. The following cartilage areas were analyzed to compute volumes: global cartilage, medial and lateral compartments, and medial and lateral femoral condyles. RESULTS: Between-reader agreement of measurements was excellent, as shown by intra-class correlation (ICC) coefficients ranging from 0.958 to 0.997 for global cartilage (P<0.0001), 0.974 to 0.998 for the compartments (P<0.0001), and 0.943 to 0.999 for the condyles(P<0.0001). Test-retest reliability of within-reader data was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001). Patient positioning reliability was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001). CONCLUSIONS: The results of this study establish the reliability of this MR imaging system. Test-retest reliability, between-reader agreement, and patient positioning reliability were all extremely high. This study represents a first step in the overall validation of an imaging system designed to follow progression of human knee OA.

Adult↗

Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juvenile rheumatoid arthritis based on pharmacokinetic modeling.

Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).

Adolescent↗

Quantifying dynamic contrast-enhanced MRI of the knee in children with juvenile rheumatoid arthritis using an arterial input function (AIF) extracted from popliteal artery enhancement, and the effect of the choice of the AIF on the kinetic parameters.

Quantification of dynamic contrast-enhanced (DCE) MRI based on pharmacokinetic modeling requires specification of the arterial input function (AIF). A full representation of the plasma concentration data, including the initial rise and decay parts, considering the delay and dispersion of the bolus contrast is important. This work deals with modeling of DCE-MRI data from the knees of children with a history of juvenile rheumatoid arthritis (JRA) by using an AIF extracted from the signal enhancement data from the nearby popliteal artery. Three models for the AIFs were considered: a triexponential (AIF1), a gamma-variate plus a biexponential (AIF2), and a biexponential (AIF3). The pharmacokinetic parameters obtained from the model were Ktrans', kep, and V'p. The results from AIF1 and AIF2 showed no statistically significant difference. However, some statistically significant differences were seen with AIF3, particularly for parameters Ktrans' and V'p in the synovium (SNVM). These results suggest the importance of obtaining an appropriate AIF representation in pharmacokinetic modeling of JRA. Specifically, the initial rising part of the AIF should be incorporated for optimal pharmacokinetic modeling results. The pharmacokinetic parameters (mean+/-SD) derived from AIF1, using the average plasma concentration data, were as follows: SNVM Ktrans'(min-1)=0.52+/-0.34, kep(min-1)=0.71+/-0.39, and V'p=0.33+/-0.16, and for the distal femoral physis (DFP) Ktrans'(min-1)=1.83+/-1.78, kep(min-1)=2.65+/-1.80, and V'p=0.46+/-0.31. The pharmacokinetic parameters in the SNVM may be useful for investigating activity and therapeutic efficacy in studies of JRA. Longitudinal studies are necessary to find or demonstrate the parameter that is more sensitive to disease activity.

Adolescent↗