Fat Lesions Research Articles

Endothelin-1 Overexpression Exacerbates Atherosclerosis and Induces Aortic Aneurysms in Apolipoprotein E Knockout Mice

Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development. Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1), Apoe(-/-) mice, and eET-1/Apoe(-/-) mice were fed high-fat diet for 8 weeks. eET-1/Apoe(-/-) had a 45% reduction in plasma high-density lipoprotein (P<0.05) and presented ≥ 2-fold more aortic atherosclerotic lesions compared with Apoe(-/-) (P<0.01). AAAs were detected only in eET-1/Apoe(-/-) (8/21; P<0.05). Reactive oxygen species production was increased ≥ 2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). Monocyte/macrophage infiltration was enhanced ≥ 2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). CD4(+) T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/Apoe(-/-) (P<0.05). The percentage of spleen proinflammatory Ly-6C(hi) monocytes was enhanced 26% by ET-1 overexpression in Apoe(-/-) (P<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/Apoe(-/-) (P<0.05) compared with Apoe(-/-). ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.

SAT0225 Do Bone Marrow Edema (BME) Lesions in the Sacroiliac Joint (SIJ) Change into Fatty Lesions Over A 3-Month Period in Patients with Axial Spondyloarthritis (AXSPA)?

BackgroundBME lesions may change into fatty lesions in the SIJ over time. In one study significant changes of fatty lesions in the SI joints were observed over 1 year in...

OP0217 Frequent Detection of Inflammation and Fat Infiltration Suggestive of Spondyloarthritis on MRI of the Entire Spine in Healthy Subjects and Patients with Mechanical Back Pain

BackgroundMechanical back pain (MBP) patients and healthy subjects may show spinal MRI lesions suggestive for spondyloarthritis (SpA) such as corner inflammatory lesions (CIL) or corner fat lesions (CFL). There are...

OP0239 What constitutes the characteristic fat lesion on MRI of the sacroiliac joints in early spondyloarthritis?

BackgroundIt is well known that fat infiltration (FI) of bone marrow may be observed on T1-weighted MRI in the sacroiliac joints (SIJ) of both healthy individuals and patients with spondyloarthritis...

SAT0250 Validation of a New Scoring Method for the Evaluation of Fat Lesions in the Spine of Patients with Axial Spondyloarthritis: The Canada-Denmark Fat Spondyloarthritis Spine Score (FASSS)

BackgroundFat lesions (FL) have been shown to follow resolution of inflammation in the spine of patients with axial spondyloarthritis (SpA) (1), and to predict development of new syndesmophytes (2). Thus,...

SAT0227 Low Diagnostic Utility Of Candidate Definitions for a Positive MRi of the Spine in Axial Spondyloarthritis

BackgroundA recent consensus statement based on a systematic literature review by the Assessment of SpondyloArthritis International Society suggested the presence of ≥3 corner inflammatory lesions (CIL) or of several corner...

Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma: characterization of five cases

To describe the imaging and histopathology of pseudomyogenic hemangioendothelioma. Five cases of pseudomyogenic hemangioendothelioma, which presented over the last 5 years, were retrieved from the files of the Royal National Orthopaedic Hospital. The imaging and histopathology were reviewed in all cases. Magnetic resonance imaging, which was available from all cases, was assessed for the following features: the number of lesions, location in soft tissue (superficial and or deep/subfascial) and bone, and the signal characteristics and morphology of individual lesions. Immunohistochemistry was performed in all cases to characterize the lesions. Four of the five patients had multiple lesions involving a single limb. Bone was involved in 3 of the 5 individuals. All tumors diffusely expressed ERG and cytokeratins AE1/3, but not MNF116. CD31 was weakly positive in 4 cases. INI-1 expression was retained in all cases. Imaging features included ill-defined, infiltrative lesions in subcutaneous fat with extension to the adjacent skin, poor- to well-defined intramuscular nodules and predominantly intracortical focal bone lesions with rare medullary involvement. Pseudomyogenic hemangioendothelioma represents a distinct recently characterized tumor type presenting in young adults, with a tendency towards multicentric bone and soft tissue involvement.

The FAt Spondyloarthritis Spine Score (FASSS): development and validation of a new scoring method for the evaluation of fat lesions in the spine of patients with axial spondyloarthritis

IntroductionStudies have shown that fat lesions follow resolution of inflammation in the spine of patients with axial spondyloarthritis (SpA). Fat lesions at vertebral corners have also been shown to predict development of new syndesmophytes. Therefore, scoring of fat lesions in the spine may constitute both an important measure of treatment efficacy as well as a surrogate marker for new bone formation. The aim of this study was to develop and validate a new scoring method for fat lesions in the spine, the Fat SpA Spine Score (FASSS), which in contrast to the existing scoring method addresses the localization and phenotypic diversity of fat lesions in patients with axial SpA.MethodsFat lesions at pre-specified anatomical locations at each vertebral endplate (C2 lower-S1 upper) were assessed dichotomously (present/absent) on spine MRIs. Two readers independently evaluated MRIs obtained at two time points for 58 patients (Exercise 1), followed by optimization of scoring methodology and reader calibration. Thereafter, the same readers read 135 pairs of MRI scans (Exercise 2; including the 58 pairs from exercise 1 randomly mixed with 77 new pairs).ResultsIn Exercise 2, the mean (SD) baseline FASSS score for the two readers was 22.5(29.6) and 21.1(28.0), respectively, and the FASSS change score was 4.2(10.6) and 6.0(12.2). Inter-reader reliability assessed as intra-class correlation coefficients (ICCs) for status and change scores were excellent (0.96 (95% CI (0.94 to 0.97)) and very good (0.86 (0.80 to 0.90)), respectively. The smallest detectable change (SDC) was 3.7 for the 135 patients. Good reliability of change scores was also observed for MRI scans conducted one year apart (ICC 0.74 (95% CI 0.44 to 0.89) and SDC 4.5). For the 58 MRI-pairs assessed in both exercises, inter-reader reproducibility for the total FASSS status score improved from very good (ICCs: 0.89 (95% CI: 0.81 to 0.93) in exercise 1 to excellent in exercise 2 (0.96 (0.93 to 0.98)), and improved substantially for the total change score (from 0.67 (0.51 to 0.80) to 0.83 (0.73 to 0.90).ConclusionsFASSS meets essential validation criteria for quantification of a common structural abnormality in clinical trials of axial spondyloarthritis.

Virtual unenhanced CT images acquired from dual-energy CT urography: Accuracy of attenuation values and variation with contrast material phase

To determine how representative virtual unenhanced (VNE) images are of true unenhanced (TNE) images when performing computed tomography (CT) urography on a dual-energy CT (DECT) system, and whether the images are affected by the contrast material phase. In this retrospective, institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study, TNE were compared with VNE images derived from the nephrographic (VNEn) and excretory (VNEe) phases in 100 consecutive CT urograms. Two readers in consensus measured attenuation values of abdominal organs, fat, and renal lesions (>1 cm). Image noise was correlated with patient thickness. Detectability of renal stones was evaluated. Image quality and acceptability was assessed using a five-point scale. Expected dose saving by removing the TNE phase was calculated. VNE attenuation values of liver, renal parenchyma, and aorta were significantly different to TNE values (p < 0.05); spleen and fat attenuation values showed no significant difference. No significant difference was found between VNEn and VNEe images. Image noise was significantly greater in TNE images (p < 0.0001) and correlated with patient thickness. VNEn and VNEe images had sensitivities of 76.6 and 65.6% for detection of stones, identifying all stones greater than 3 and 4 mm, respectively. Both VNE images received significantly lower image quality scores than TNE images (p < 0.0001); however, the majority of images were deemed acceptable. The mean theoretical dose saving by removing the TNE phase was 35%. Although VNE images demonstrate high reader acceptability, accuracy of attenuation values and detection of small stones is limited. The contrast material phase, however, does not affect attenuation values. Further validation of VNE images is recommended prior to clinical implementation.

1658P - Diffuse Reflectance Spectroscopy; Towards Clinical Application in Breast Cancer

ABSTRACT Background Diffuse reflectance spectroscopy (DRS) is a promising new technique for breast cancer diagnosis. During DRS tissue is illuminated by a selected light spectrum. By specific absorption and scattering characteristics of the tissue an ‘optical fingerprint’ is obtained which represents specific morphological information. In this way DRS is able to differentiate normal tissue from tumor tissue. Here we compared the diagnostic accuracy of DRS in a cohort of patients and each patient individually to the pathology analysis of normal and malignant breast tissue. Methods Breast tissue from 47 female patients was analysed ex-vivo by DRS. A total of 1073 optical spectra were collected from fat, glandular tissue and fibroadenoma lesions as well as from (pre)-malignant tissue samples. These spectra were analyzed for each patient individually as well as for all patients collectively. Results were compared to the pathology analysis of biopsies from each measurement location. Results Collective patient data analysis for discrimination between normal and malignant breast tissue resulted in a sensitivity of 90%, a specificity of 88% and an overall accuracy of 89%. For individual analysis all measurements per patient were categorized as either benign or malignant. The discriminative accuracy of this individual analysis was nearly 100%. When an arbitrary threshold was used of a 90% agreement between all DRS measurements and the pathology analysis for each individual patient to ascertain a diagnosis, only in one patient the diagnosis was classified as uncertain. Conclusions Our results demonstrate that diffuse reflectance spectroscopy can be considered as an important new optical sensing technique that could improve the diagnostic workflow in breast cancer. Disclosure All authors have declared no conflicts of interest.

Measuring of the maximum fat lesion ratio

Measuring of the maximum fat lesion ratio

Suppression of inflammation and effects on new bone formation in ankylosing spondylitis: evidence for a window of opportunity in disease modification

ObjectivesAlthough MRI data supports a link between spinal inflammation and formation of new bone in ankylosing spondylitis, anti-tumour necrosis factor α therapies have not been shown to prevent new bone...

Association of pericardial fat and coronary high-risk lesions as determined by cardiac CT

ObjectivePericardial adipose tissue (PAT) is a pathogenic fat depot associated with coronary atherosclerosis and cardiovascular events. We hypothesized that higher PAT is associated with coronary high-risk lesions as determined by cardiac CT. MethodsWe included 358 patients (38% female; median age 51 years) who were admitted to the ED with acute chest pain and underwent 64-slice CT angiography. The cardiac CT data sets were assessed for presence and morphology of CAD and PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at least two of the following characteristics: positive remodeling, low-density plaque, and spotty calcification. PAT was defined as any pixel with CT attenuation of −190 to −30HU within the pericardial sac. ResultsBased on cardiac CT, 50% of the patients (n=180) had no CAD, 46% (n=165) had CAD without high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT in patients with high-risk lesions was significantly higher compared to patients without high-risk lesions and without any CAD (151.9 [109.0–179.4]cm3 vs. 110.0 [81.5–137.4]cm3, vs. 74.8 [58.2–111.7]cm3, respectively p=0.04 and p<0.0001). These differences remained significant after adjusting for traditional risk factors including BMI (all p<0.05). The area under the ROC curve for the identification of high-risk lesions was 0.756 in a logistic regression model with PAT as a continuous predictor. ConclusionPAT volume is nearly twice as high in patients with high-risk coronary lesions as compared to those without CAD. PAT volume is significantly associated with high risk coronary lesion morphology independent of clinical characteristics and general obesity.

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

Focal fat infiltration is frequently visible on magnetic resonance imaging (MRI) of the spine in patients with ankylosing spondylitis (AS) and likely reflects postinflammatory tissue metaplasia. To support the concept of coupling between inflammation and new bone formation, we tested the hypothesis that focal fat infiltration at a vertebral corner is more likely to evolve into a de novo syndesmophyte. MRI scans were obtained at baseline and radiographs were obtained at baseline and 2 years in 100 AS patients from 2 cohorts: a clinical trial cohort (n = 38) and an observational cohort (n = 62). In the clinical trial cohort, patients were randomized to receive anti-tumor necrosis factor (anti-TNF) therapy or placebo for 12-24 weeks and then open-label treatment for 2 years. In the observational cohort, patients received either standard therapy (n = 36) or anti-TNF therapy (n = 26) for 2 years. Vertebral corner inflammation and fat infiltration were assessed independently by pairs of readers who were blinded with regard to the radiographic findings. New syndesmophytes developed significantly more frequently in vertebral corners with fat in both the clinical trial (10.2%) and the observational (6.5%) cohort as compared to those without either feature on baseline MRI (3.1% [P = 0.008] and 1.4% [P = 0.0002], respectively). Adjusting for within-patient variations in baseline syndesmophytes/ankylosis, vertebral corners that were fat-positive/inflammation-positive significantly predicted new syndesmophytes, with an odds ratio (OR) of 7.6 (95% confidence interval [95% CI] 1.5-38.5 [P = 0.01]), while a model that included baseline variations in both fat and inflammation showed an OR of 5.8 (95% CI 2.2-15.3 [P < 0.001]) for inflammation and an OR of 1.9 (95% CI 0.9-4.1 [P = 0.1]) for fat. Our data lend support to the hypothesis that inflammatory lesions evolve into new bone through a process of tissue metaplasia that includes fat infiltration.

A role for elastography in the diagnosis of breast lesions by measuring the maximum fat lesion ratio (max-FLR) by tissue Doppler imaging

The role of elastography for breast tumors is still ambiguous. The purpose of this study was to inquire how effectively elastography can be used in the diagnosis of breast tumors. The fat lesion ratio (FLR) of 244 lesions (99 malignant and 145 benign lesions) was calculated using tissue Doppler imaging with elastography. The pathological confirmations were performed by core needle or excisional biopsy. Conventional ultrasonography (US) findings were classified according to the Breast Imaging Reporting and Data System. We tried to set the region of interest (ROI) at the hardest area of the target and measured the maximum FLR (max-FLR) of the target with elastography, whereas the control ROI was placed in the subcutaneous adipose tissue. The diagnostic potential of the max-FLR combined with the US category was evaluated. The mean max-FLR of malignant lesions was significantly greater than that of benign lesions, at 11.0 and 4.4, respectively (p < 0.01). The max-FLR showed a wide overlap range between benign and malignant lesions, but there were no malignant lesions showing a less than 2.0 max-FLR. Ninety-six percent of the lesions interpreted as category 3 were benign, and the negative predictive value measuring the max-FLR was kept at 98% as long as the max-FLR was less than 4.0. Measuring the max-FLR may reduce unnecessary biopsies by 57.5% in the category 3 group. Combining conventional US categories and measuring max-FLR with elastography may be helpful in reducing the number of unnecessary biopsies in category 3 lesions.

Reduced test-day milk fat percentage in cows diagnosed with claw horn lesions during routine claw trimming

The objective of this study was to investigate whether cows diagnosed with claw horn lesions during routine claw trimming had an altered milk fat percentage on test days preceding the diagnosis, compared with cows without such lesions. Data included date of trimming, cow number, type, and location of claw lesions recorded by a professional claw trimmer during routine trimming sessions on 11 commercial dairy farms, and monthly test-day data. Recordings from 4,381 cows were included in the analysis. Three hundred seventy-two (8.5%) cows were diagnosed with at least one claw lesion. One hundred ninety-five (4.4%) cows were classified as cases of laminitis and 169 cows (3.9%) were classified as cases of infectious claw diseases. Average test-day milk fat percentage was estimated from monthly test-day data using a mixed model with a random farm effect and a marginal effect for repeated measurements. Estimated milk fat percentage of cows classified as cases of laminitis on the day of claw trimming was 0.17 and 0.22% less than that of cows with either no claw lesion or those with an infectious claw disease, on test days occurring 2 and 5 mo before claw trimming, respectively. To the best of our knowledge, decreased test-day milk fat percentage in dairy cows diagnosed with claw horn lesions has not been described. Because decreased milk fat and claw horn lesions have both been associated with subacute ruminal acidosis, it is plausible that subacute ruminal acidosis played a role in the association we found. A prospective study with a greater frequency of claw examinations would be necessary to help clarify these associations. Our findings indicate that test-day milk fat might be useful as a tool for monitoring cows and farms at risk for claw horn lesions.

The role of cytochrome P-4502E1 in the development of hepatic fat, fibrosis and DNA lesions in patients with of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD)

The role of cytochrome P-4502E1 in the development of hepatic fat, fibrosis and DNA lesions in patients with of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD)

Interim-PET Scan Interpretation In the Ongoing Prospective Clinical Trial HD 0607, In Advanced-Stage Hodgkin Lymphoma: Results of the the Expert Panel Review

AbstractAbstract 3891 Background:several PET response-adapted prospective clinical trials are running at the moment, aimed at assessing the role of chemotherapy intensification in ABVD-treated Hodgkin Lymphoma (HL) patients with interim PET-positive after 2 cycles (PET-2). Standard interim-PET interpretation rules are still lacking, and expert review panels for PET interpretation have been implemented in these trials. We report here the results of PET-2 review in the HD 0607 trial. Patients and methods:starting from July 2008 till now, 236 advanced-stage HL patients have been consecutively enrolled in the Italian GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter clinical trial HD 0607 (NCT Identifier: NCT00795613). Advanced-stage (IIB-IVB) HL patients are first treated with 2 ABVD courses and PET-2 performed afterwards. All the non-negative PET-2 scan are reviewed by the expert panel. Non-negative PET-2 is defined as any scan with any residual FDG uptake outside the physiological areas of the tracer concentration. All the non-negative PET-2 according to the local centers (PET-2loc) are uploaded on the dedicated website (http://magic5.to.infn.it/gitil), along with the baseline scans. Six independent reviewers re-interpret the scans according to the 5-point semiquantitative score with mediastinum and liver as reference organs for residual fluorodeoxyglucose (FDG) uptake (Deauville score, Meignan 2009). The first three reviewers replying within 72 hours from PET upload determine the panel final decision; the remaining three report the scans later. Patients with a score 4 or 5 shifted to BEACOPP or Rituximab-BEACOPP escalated treatment; patients with score 1–3 continued with ABVD. Patient with bulky lesion (defined as a nodal mass with the largest diameter 3 6 cm) were treated with IF-RT. Results:199/236 patients performed a PET-2 scan: 131 (66%) showed a negative, 68 (33%) a non-negative scan. These 68 PET-2loc were reviewed (PET-2rev.); the clinical characteristics of patients with a reviewed and unreviewed PET-2loc were the following: mean age 32 vs.35, Stage III 19/68 (28%) and 61/131(46%), Stage IV 26/68 (39%) and 45/131 (34%), Bulky 44/68 (65%) and 93/131 (71%), IPS 3 or more 20/68 (29%) and 20/131 (15%), respectively. As a result of review there were 32 positive PET-2rev. and 36 negative PET-2rev. The median PET-2 review time from the uploading in the website to the third reviewer's report was 48 hours (1-90). The 32 positive PET-2rev scans showed a single residual focus in 28 and multiple foci of residual FDG uptake in 4 cases (all score 5). 22 showed a single lesion in the mediastinum, 4 in superficial lymph nodes and 2 in the lung. In 25/28 (89%) patients the single residual FDG uptake was within a bulky lesion and in 3/28 was outside it. The concordance rate among couples of reviewers for a positive vs. negative scan, measured with Cohen's Kappa, ranged between 0.76 (substantial agreement) and 0.92 (almost perfect agreement). The overall concordance rate measured with Krippendorf's Alpha, (assuming chance = 0 and perfect agreement =1) was 0.82. Lower concordance among reviewers was found in scans showing FDG residual uptake in anatomical structures not clearly related to lymphoma (brown fat, large vessels, bowel, tonsil, and inflammatory lung lesions). Conclusions:these data show that (1) the preliminary reports of a very high binary and overall concordance rate among reviewers using the Deauville score for PET-2 reporting (Barrington 2010) have been confirmed; (2) the online review process for PET-2 scan is feasible and simple; (3) most of the positive PET-2 scan showed a residual FDG uptake in the site of bulky disease, mostly in mediastinum. Disclosures:No relevant conflicts of interest to declare.

Region-based diagnostic performance of multidetector CT for detecting peritoneal seeding in ovarian cancer patients

To determine the accuracy of multi-detector CT (MDCT) compared with the surgical findings, such as peritoneal seeding and metastatic lymph nodes, in ovarian cancer patients. Fifty-seven FIGO stage IA-IV ovarian cancer patients, who underwent MDCT before primary surgery, were included in this study. Two radiologists evaluated the following imaging findings in consensus: the presence of nodular, plaque-like or infiltrative soft-tissue lesions in peritoneal fat or on the serosal surface; presence of ascites; parietal peritoneal thickening or enhancement; and small bowel wall thickening or distortion. We also evaluated the presence of lymph node metastases. To allow region-specific comparisons, the peritoneal cavity was divided into 13 regions and retroperitoneal lymph nodes were divided into 3 regions. Descriptive statistical data were thus obtained. The MDCT sensitivity, specificity, positive predictive values, and negative predictive values were 45, 72, 46, and 72%, respectively, for detecting peritoneal seeding and 21, 90, 52, and 69%, respectively, for detecting lymph node metastasis. MDCT is moderately accurate for detecting peritoneal metastasis and lymph node metastasis in ovarian cancer patients.

Reevaluation of Renal Cell Carcinoma and Perirenal Fat Invasion Only

Controversy continues over whether perirenal fat invasion in pT3a renal cell carcinoma is a prognostic factor. We investigated the prognosis of renal cell carcinoma with perirenal fat invasion compared to the prognosis of other pathological stages by tumor size. We reviewed the medical records of 946 patients who underwent curative surgery for pT1-pT3bN0M0 renal cell carcinoma between 1988 and 2006. Patients with pT3a stage disease and perirenal fat invasion only were divided into 2 subgroups by a 7 cm tumor size cutoff. The prognostic impact of perirenal fat invasion on disease-free and cancer specific survival was investigated. Patients with perirenal fat invasion and lesions greater than 7 cm had lower 5-year disease-free (49.5% vs 77.2%, p = 0.004) and cancer specific (58.5% vs 95.6%, p = 0.003) survival than those with lesions 7 cm or less. Patients with perirenal fat invasion and lesions 7 cm or less had similar 5-year disease-free and cancer specific survival compared to those with pT1 tumors (p = 0.109 and 0.602, respectively). For tumors 7 cm or less multivariate analysis showed that perirenal fat invasion was not a significant predictor of disease-free (p = 0.119) or cancer specific (p = 0.208) survival. In contrast, perirenal fat invasion was an independent prognostic factor for disease-free (p = 0.002) and cancer specific (p = 0.027) survival in patients with tumors greater than 7 cm. Findings suggest that the prognostic significance of perirenal fat invasion depends on primary tumor size. Perirenal fat invasion included in the pT3a stage regardless of tumor size should be reevaluated by tumor size for a more accurate patient prognosis.