Measurement of pancreatic cystic lesions on magnetic resonance imaging: efficacy of standards in reducing inter-observer variability

Purpose

The purpose of this study is to assess inter-observer variability in the measurement of pancreatic cystic lesions with MRI and to determine the impact of measurement standards.

Materials and methods

In this IRB-approved, HIPAA-compliant study with waiver of informed consent, 144 MRI examinations, containing pancreatic cystic lesions measuring between 5 and 35 mm, were reviewed independently by two radiology attendings and two abdominal imaging fellows. Measurements were repeated by the same reviewers 12 weeks later after the introduction of measurement standards. Results were analyzed using within-subject standard deviation, intraclass correlation coefficient, and kappa.

Results

Prior to standardization, the within-subject standard deviation, showing measurement variability in each cyst, was 4.0 mm, which was reduced to 3.3 mm after introduction of measurement standards (p < 0.01). Overall inter-observer agreement, kappa, improved from 0.59 to 0.65 (p = 0.04). The frequency of all four reviewers agreeing on size category increased from 51% to 60%. The intraclass correlation coefficient increased from 0.81 to 0.86.

Conclusions

There is significant and frequent inter-observer variability in the measurement of pancreatic cystic lesions with MRI which could affect clinical management. Implementation of measurement standards reduces measurement variability and aids in preventing erroneous reporting of growth and potentially unwarranted changes in management.

     

Obesity is associated with neutrophil dysfunction and attenuation of murine acute lung injury

Although obesity is implicated in numerous health complications leading to increased mortality, the relationship between obesity and outcomes for critically ill patients appears paradoxical. Recent studies have reported better outcomes and lower levels of inflammatory cytokines in obese patients with acute lung injury (ALI)/acute respiratory distress syndrome, suggesting that obesity may ameliorate the effects of this disease. We investigated the effects of obesity in leptin-resistant db/db obese and diet-induced obese mice using an inhaled LPS model of ALI. Obesity-associated effects on neutrophil chemoattractant response were examined in bone marrow neutrophils using chemotaxis and adoptive transfer; neutrophil surface levels of chemokine receptor CXCR2 were determined by flow cytometry. Airspace neutrophilia, capillary leak, and plasma IL-6 were all decreased in obese relative to lean mice in established lung injury (24 h). No difference in airspace inflammatory cytokine levels was found between obese and lean mice in both obesity models during the early phase of neutrophil recruitment (2-6 h), but early airspace neutrophilia was reduced in db/db obese mice. Neutrophils from uninjured obese mice demonstrated diminished chemotaxis to the chemokine keratinocyte cytokine compared with lean control mice, and adoptive transfer of obese mouse neutrophils into injured lean mice revealed a defect in airspace migration of these cells. Possibly contributing to this defect, neutrophil CXCR2 expression was significantly lower in obese db/db mice, and a similar but nonsignificant decrease was seen in diet-induced obese mice. ALI is attenuated in obese mice, and this blunted response is in part attributable to an obesity-associated abnormal neutrophil chemoattractant response.     

Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice

Disruption of intracellular calcium homeostasis via abnormal and excessive activation of ryanodine receptors plays an important role in the neuropathology of Alzheimer's disease. We investigated the therapeutic effect of dantrolene, a ryanodine receptor antagonist, on cognitive dysfunction and neuropathology in the triple transgenic Alzheimer mouse model (3xTg-AD). 3xTg-AD mice were treated with dantrolene from 2 to 13 months of age. Learning and memory were measured with the Morris Water Maze at 6, 10, and 13 months of age. Amyloid and tau neuropathology and biomarkers for synaptic dysfunction and neurodegeneration were examined in the brain using immunoblotting or immunohistochemistry. Dantrolene treatment for 11 months significantly reduced both memory deficits and amyloid plaque load in the hippocampus in 13-month-old 3xTg-AD mice. Dantrolene treatment, however, had no effect on phosphorylated tau, phosphorylated or total GSK-3β, synaptic markers, or mitochondrial or cytosolic cytochrome C. Our results suggest that dantrolene significantly improves cognition in a murine model of Alzheimer's disease and is associated with a reduction in amyloid plaque burden, forming the basis for a novel therapeutic approach for Alzheimer's disease.     

Distinct immunophenotype of early T-cell progenitors in T lymphoblastic leukemia/lymphoma may predict FMS-like tyrosine kinase 3 mutations

FMS-like tyrosine kinase 3 (FLT3) mutation in T lymphoblastic leukemia/lymphoma (T-LL) is rare (～4%) and reported only in cases with CD117 expression. This study aimed to identify the immunophenotypic features that may predict FLT3 mutations. We report 3 (43%) of 7 CD117(+) T-LL cases harboring FLT3-internal tandem duplication mutation. Compared with 4 FLT3-unmutated cases, all 3 FLT3-mutated cases had a distinct immunophenotype (CD1a(-)/CD2(+)/CD7(+)/CD34(+)/CD117(uniform+)/Tdt(+)) corresponding to the stage of earliest thymic T-cell progenitors possessing myeloid lineage potential. Indeed, all FLT3-mutated T-LL cases expressed myeloperoxidase on a very small subset of blasts and, thus, may be further considered a mixed phenotype acute leukemia, T/myeloid, by the 2008 World Health Organization classification scheme. We conclude that this unique immunophenotype (CD1a(-)/CD2(+)/CD7(+)/CD34(+)/CD117(+)/Tdt(+)) is a better predictor of FLT3 mutation than sole CD117 expression.     

Region-of-interest reconstruction of motion-contaminated data using a weighted backprojection filtration algorithm

The recently developed weighted backprojection filtration (WBPF) algorithm using data redundancy has capabilities that make this algorithm an attractive candidate for reconstructing images from motion-contaminated projection data. First, the WBPF algorithm is capable of reconstructing region-of-interest (ROI) images from reduced-scan fan-beam data, which have less data than the short-scan data required to reconstruct the entire field of view (FOV). Second, this algorithm can reconstruct ROI images from truncated data. Using phantom simulation studies, we demonstrate how these unique capabilities can be exploited to reduce the amount of motion-contaminated data used for reconstruction. In particular, we use examples from cardiac imaging to illustrate how off-center phantom positioning combined with phase-interval ROI reconstruction can result in the suppression of motion artifacts. In terms of temporal resolution, reduced-scan reconstruction with 45% of a full-scan dataset can be used to improve the temporal resolution of a short-scan reconstruction by 25.8% if ungated data are used. For data gated at 66 beats per minute, reduced-scan reconstruction with 45% of a full-scan dataset can be used to improve the temporal resolution of a short-scan reconstruction by 7.9%. As a result of our studies, we believe that the WBPF algorithm demonstrates the potential for reconstructing quality ROI images from motion-contaminated fan-beam data.     

DCEMRI of breast lesions: is kinetic analysis equally effective for both mass and nonmass-like enhancement?

To perform a pilot study investigating whether the sensitivity and specificity of kinetic parameters can be improved by considering mass and nonmass breast lesions separately. The contrast media uptake and washout kinetics in benign and malignant breast lesions were analyzed using an empirical mathematical model (EMM), and model parameters were compared in lesions with mass-like and nonmass-like enhancement characteristics. 34 benign and 78 malignant breast lesions were selected for review. Dynamic MR protocol: 1 pre and 5 postcontrast images acquired in the coronal plane using a 3D T1-weighted SPGR with 68 s timing resolution. An experienced radiologist classified the type of enhancement as mass, nonmass, or focus, according to the BI-RADS lexicon. The kinetic curve obtained from a radiologist-drawn region within the lesion was analyzed quantitatively using a three parameter EMM. Several kinetic parameters were then derived from the EMM parameters: the initial slope (Slope(ini)), curvature at the peak (kappa(peak)), time to peak (T(peak)), initial area under the curve at 30 s (iAUC30), and the signal enhancement ratio (SER). The BI-RADS classification of the lesions yielded: 70 mass lesions, 38 nonmass, 4 focus. For mass lesions, the contrast uptake rate (alpha), contrast washout rate (beta), iAUC30, SER, Slope(ini), T(peak) and kappa(peak) differed substantially between benign and malignant lesions, and after correcting for multiple tests of significance SER and T(peak) demonstrated significance (p < 0.007). For nonmass lesions, we did not find statistically significant differences in any of the parameters for benign vs. malignant lesions (p > 0.5). Kinetic parameters could distinguish benign and malignant mass lesions effectively, but were not quite as useful in discriminating benign from malignant nonmass lesions. If the results of this pilot study are validated in a larger trial, we expect that to maximize diagnostic utility, it will be better to classify lesion morphology as mass or nonmass-like enhancement prior to kinetic analysis.     

Host response to implanted porcine-derived biologic materials in a primate model of abdominal wall repair

Three commercially available porcine-derived biologic meshes were implanted in an Old World primate abdominal wall resection repair model to compare biological outcome as a predictor of clinical efficacy. Tissues were explanted over a 6-month period and evaluated for gross pathology, wound healing strength, mesenchymal cellular repopulation, vascularity, and immune response. In vivo functional outcomes were correlated with in vitro profile for each material. Small intestinal submucosa-based implants demonstrated scar tissue formation and contraction, coincident with mesh pleating, and were characterized by immediate and significant cellular and humoral inflammatory responses. Porcine dermal-based grafts demonstrated significant graft pleating, minimal integration, and an absence of cellular repopulation and vascularization. However, a significant cellular immune response surrounded the grafts, coincident with poor initial wound healing strengths. In vivo observations for the three porcine-derived mesh products correlated with individual in vitro profiles, indicating an absence of characteristic biochemical markers and structural integrity. This correlation suggests that in vivo results observed for these mesh products are a direct consequence of specific manufacturing processes that yield modified collagen matrices. The resulting loss of biological and structural integrity elicits a foreign body response while hindering normal healing and tissue integration.