Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla.

OBJECTIVE: Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis. METHODS: We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO2) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical-histological data were measured by correlation coefficients. RESULTS: Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r = -0.51, p = 0.02) and excellently on day 28 (r = -0.84, p = 0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r = 0.49, p = 0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r = 0.89, p = 0.04; r = 1.0, p < 0.0001) with histological scores in arthritic knees. CONCLUSION: The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields. KEY POINTS: • BOLD and DCE MRI detect interval perisynovial changes in a rabbit knee • BOLD and DCE MRI act as surrogate markers of physiologic changes in arthritis • BOLD MRI signal represents oxygen extraction compared with intra-articular PO 2 • DCE MRI measurements estimate physiologic periarticular vascular properties • In rabbit knees with acute arthritis, BOLD/DCE MRI highly correlated with histological scores.

Systematic protocol for assessment of the validity of BOLD MRI in a rabbit model of inflammatory arthritis at 1.5 tesla.

BACKGROUND: Blood-oxygen-level-dependent (BOLD) MRI has the potential to identify regions of early hypoxic and vascular joint changes in inflammatory arthritis. There is no standard protocol for analysis of BOLD MRI measurements in musculoskeletal disorders. OBJECTIVE: To optimize the following BOLD MRI reading parameters: (1) statistical threshold values (low, r > 0.01 versus high, r > 0.2); (2) summary measures of BOLD contrast (percentage of activated voxels [PT%] versus percentage signal difference between on-and-off signal intensities [diff_on_off]); and (3) direction of BOLD response (positive, negative and positive + negative). MATERIALS AND METHODS: Using BOLD MRI protocols at 1.5 T, arthritic (n = 21) and contralateral (n = 21) knees of 21 juvenile rabbits were imaged at baseline and on days 1, 14 and 28 after a unilateral intra-articular injection of carrageenan. Nine non-injected rabbits served as external control knees (n = 18). By comparing arthritic to contralateral knees, receiver operating characteristic curves were used to determine diagnostic accuracy. RESULTS: Using diff_on_off and positive + negative responses, a threshold of r > 0.01 was more accurate than r > 0.2 (P = 0.03 at day 28). Comparison of summary measures yielded no statistically significant difference (P > 0.05). Although positive + negative (AUC = 0.86 at day 28) and negative responses (AUC = 0.90 at day 28) for PT% were the most diagnostically accurate, positive + negative responses for diff_on_off (AUC = 0.78 at day 28) also had acceptable accuracy. CONCLUSIONS: The most clinically relevant reading parameters included a lower threshold of r > 0.01 and a positive + negative BOLD response. We propose that diff_on_off is a more clinically relevant summary measure of BOLD MRI, while PT% can be used as an ancillary measure.

Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis.

BACKGROUND: Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis. OBJECTIVE: To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis. MATERIALS AND METHODS: Rabbit knees were injected with albumin (n=9) or saline (n=6) intra-articularly, or were not injected (control knees, n=9). Except for two rabbits (albumin-injected, n=2 knees; saline-injected, n=2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30 s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers. RESULTS: Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P=0.04). For albumin-injected knees (P<0.05) and among different categories of knees (P=0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P=0.047; saline-injected, P=0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P=0.07). CONCLUSION: As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis.

Myeloid sarcoma of the vagina: a report of 2 cases.

OBJECTIVE: To describe 2 cases of myeloid sarcoma of the vagina, in a patient without a history of acute myeloid leukemia (AML) and in another whose condition was previously diagnosed with AML. MATERIALS AND METHODS: The clinical histories of 2 patients whose conditions were diagnosed with myeloid sarcoma of the vagina were obtained from their medical records. RESULTS: Case 1: A 77-year-old woman with no systemic illnesses presented with a vaginal lump. Clinically, there was a 6-cm periurethral mass that was examined by biopsy. The histopathologic specimen was evaluated on routine and immunohistochemical stains, and myeloid sarcoma was diagnosed after extensive immunohistochemical analysis. The patient was treated with pelvic radiation. She developed extensive myeloid sarcoma of the skin and AML 4.5 months later; she died 2 weeks later, 5 months after the initial presentation. Case 2: A 36-year-old woman with a known history of AML who has had multiple leukemic and extramedullary recurrences presented with a pelvic mass. Physical findings revealed large masses in the vagina and rectovaginal septum, which were confirmed as myeloid sarcoma after biopsy and histologic examination. The patient was treated with pelvic/vaginal radiation. Five months later, she had another leukemic relapse and died within 1 day of palliative chemotherapy. CONCLUSIONS: Myeloid sarcoma of the vagina is extremely rare. Most patients have a poor prognosis and either have a history of or will subsequently develop AML.

Contrast-enhanced triggered harmonic sonography for assessment of periarticular hemodynamic changes in experimental arthritis.

BACKGROUND: Objective quantification is critical for assessment of functional sonography in inflammatory arthritis. To create a microbubble contrast-enhanced image of vessels that lie below the resolution of a standard US system, a technique is required that detects preferentially the contrast agent echo, rejecting that from background tissue: harmonic imaging. OBJECTIVES: To investigate the ability of contrast-enhanced triggered harmonic sonography (CETHS) to evaluate periarticular hemodynamic changes over the course of experimental arthritis and to discriminate presence and absence of arthritis based on measurement values obtained at specific time-points. MATERIALS AND METHODS: Arthritis was induced in rabbits knees by intra-articular injection of serum bovine albumin, which acted as an antigen. A total of 11 rabbits (8 with unilateral arthritis and 3 control animals) were imaged at 0, 1, 7, 14, 21 and 28 days of antigen-induced arthritis and euthanized at 28 days. A continuous infusion protocol was performed (triggering times 30.0, 20.0, 10.0, 5.0, 2.0, 1.0, and 0.5 s). Hemodynamic indices of synovial microvasculature (vascular volume, mean velocity and flow rate) were obtained and compared with clinical, laboratory, and histological surrogate markers. RESULTS: Although interval CETHS changes were noted for flow rate (P=0.007) and vascular volume (P=0.003) ratios in albumin-injected knees, no significant differences in ratios were identified over time between albumin-injected and non-injected knees for flow rate (P=0.52), vascular volume (P=0.23) and mean velocity (P=0.19). Flow rate most accurately differentiated between presence and absence of arthritis according to clinical measurements in early (day 1) arthritis, and mean velocity in mid-term arthritis (day 14; both P=0.02). CONCLUSION: Although the measurement properties of CETHS indices were poor in the evaluation of hemodynamic differences over time in albumin-injected knees compared with non-injected knees, they enabled discrimination between presence and absence of arthritis at specific time-points in different stages.

Dynamic contrast-enhanced MRI quantification of synovium microcirculation in experimental arthritis.

OBJECTIVE: Our objective was to analyze MRI contrast-enhancement patterns in arthritic and nonarthritic knees and the relationship of those patterns with clinical, laboratory, and histologic synovium markers. MATERIALS AND METHODS: Dynamic contrast-enhanced MRI was performed in nine arthritic and three nonarthritic knees of juvenile rabbits. A two-compartment pharmacokinetic model of signal intensity-time data was implemented to generate parametric maps of signal slope, maximal percentage of signal change, capillary permeability, leakage space volume, and time-to-peak. MRI values were compared with clinical, laboratory, and histologic markers for evaluation of synovial changes during the progression of arthritis. RESULTS: Parametric maps of capillary permeability and signal slope depicted significant differences between arthritic and nonarthritic knees. Arthritic knees showed increased capillary permeability (p = 0.006) and signal slope (p = 0.01) with time after onset of disease as opposed to nonarthritic knees (permeability, p = 0.65; slope, p = 0.56). Significant correlations were found between temporal changes in capillary permeability (p = 0.002), signal slope (p = 0.003), and serum concentrations of amyloid A. No relationship was noted between any MRI parameters and histologic scores. The discriminative power of MRI indexes varied according to the stage of arthritis: time-to-peak was most accurate for differentiation of presence versus absence of arthritis in early arthritis (day 1, p = 0.0002), and signal slope was most accurate in midterm arthritis (day 14, p = 0.001). CONCLUSION: In vivo capillary permeability and signal slope have distinctive dynamic MRI properties. The accuracy of MRI parameters for diagnostic evaluation of experimental arthritis differs according to the stage of disease.