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Background Advances in abdominal MRI have enabled rapid, free-breathing imaging without the need for intravenous or oral contrast material. The use of MRI as the primary imaging modality for suspected appendicitis has not been previously studied. Purpose To determine the diagnostic performance of MRI as the initial imaging modality in children suspected of having acute appendicitis. Materials and Methods The study included consecutive patients 18 years of age and younger presenting with acute abdominal pain at a tertiary care institution from January 2013 through June 2016 who subsequently underwent an unenhanced MRI examination as the primary diagnostic imaging modality. Electronic medical records and radiology reports were retrospectively evaluated for the feasibility and diagnostic performance of MRI, with surgical pathology and follow-up electronic records as reference standards. Statistical analyses were performed by using simple binomial proportions to quantify sensitivity, specificity, and accuracy, and exact 95% confidence intervals (CIs) were obtained. Results After exclusions, 402 patients (median age: 13 years; interquartile range [IQR], 9-15 years; 235 female patients; 167 male patients) were included. Sedation for MRI was required in 13 of 402 patients (3.2%; 95% CI: 1.7%, 5.5%). The appendix was visualized in 349 of 402 patients (86.8%; 95% CI: 83.1%, 90%); for the remaining patients, a diagnosis was provided on the basis of secondary signs of appendicitis. The sensitivity, specificity, and accuracy of MRI as the primary diagnostic imaging modality for the evaluation of acute appendicitis were 97.9% (95 of 97; 95% CI: 92.8%, 99.8%), 99% (302 of 305; 95% CI: 97.2%, 99.8%), and 98.8% (397 of 402; 97.1%, 99.6%), respectively. Among patients with negative findings for appendicitis at MRI, an alternate diagnosis was provided in 113 of 304 patients (37.2%; 95% CI: 31.7%, 42.9%). Conclusion When performed as the initial imaging modality in children suspected of having acute appendicitis, MRI examinations had high diagnostic performance for the diagnosis of acute appendicitis and in providing alternative diagnoses. © RSNA, 2019 See also the editorial by Dillman and Trout in this issue.

Background: T 1 mapping is often used in some clinical protocols. Existing techniques are limited in slice coverage, and/or spatial-temporal resolution, or require long acquisitions. Here we present a multi-slice inversion-recovery (IR) radial steady-state free precession (radSSFP) pulse sequence combined with a principal component (PC) based reconstruction that overcomes these limitations., Purpose: To develop a fast technique for multi-slice high-resolution T 1 mapping., Study Type: Technical efficacy study done prospectively., Phantom/subjects: IR-radSSFP was tested in phantoms, five healthy volunteers, and four patients with abdominal lesions., Field Strength/sequence: IR-radSSFP was implemented at 3T., Assessment: Computer simulations were performed to optimize the flip angle for T 1 estimation; testing was done in phantoms using as reference an IR spin-echo pulse sequence. T 1 mapping with IR-radSSFP was also assessed in vivo (brain and abdomen) and T 1 values were compared with literature. T 1 maps were also compared with a radial IR-FLASH technique., Statistical Tests: A two-tailed t-test was used to compare T 1 values in phantoms. A repeatability study was carried out in vivo using Bland-Altman analysis., Results: Simulations and phantom experiments showed that a flip angle of 20˚ was optimal for T 1 mapping. When comparing single to multi-slice experiments in phantoms there were no significant differences between the means T 1 values (P = 0.0475). In vivo results show that T 1 maps with spatial resolution as high as 0.69 mm × 0.69 mm × 2.00 mm (brain) and 0.83 mm × 0.83 mm × 3.00 mm (abdomen) can be generated for 84 brain slices in 3 min and 10 abdominal slices in a breath-hold; T 1 values were comparable to those reported in literature. The coefficients of variation from the repeatability study were 1.7% for brain and 2.5-2.7% in the abdomen., Data Conclusion: A multi-slice IR-radSSFP technique combined with a PC-based reconstruction was demonstrated for higher resolution T 1 mapping. This technique is fast, motion-insensitive and yields repeatable T 1 values comparable to those in literature., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:239-252., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: We systematically analyzed the extent of disease in unifocal invasive lobular carcinoma (ILC) using ultrasonography, with the histopathologic findings as the reference standard., Patients and Methods: In the present single-institution retrospective study, 128 cases of ILC were identified during a 5-year period. After exclusions, the analyzed cohort included 66 cases. Ultrasound measurements of the tumor extent along 3 axes were obtained. The tumor size was determined as the largest extent among the 3 axes and the tumor volume by ellipsoidal approximation. Pathology review provided the tumor size and volume. Correlation and regression analyses of tumor size and volume from the ultrasound and pathologic examinations were performed. The tumor stage from the ultrasound and pathologic examinations were used for the concordance analyses., Results: The median and quartiles (Q1, Q3) of tumor size from ultrasonography and pathology were 12.5 mm (Q1, 9 mm; Q3, 19 mm) and 17 mm (Q1, 12 mm; Q3, 25 mm), respectively. The corresponding data for tumor volume were 0.52 cm 3 (Q1, 0.18 cm 3 ; Q3, 1.92 cm 3 ) and 1.04 cm 3 (Q1, 0.45 cm 3 ; Q3, 2.49 cm 3 ). The ultrasound measurements correlated with the pathology-reported tumor size (Spearman ρ = 0.678; P < .0001) and volume (Spearman ρ = 0.699; P < .0001). The ultrasound-measured size and volume differed from the pathology-reported size and volume (P < .0001; Wilcoxon signed ranks test). Concordance between the clinical tumor size stage from ultrasound (cT) and pathology tumor size stage (pT) varied with the pT stage (P = .0003, Fisher's exact test), with the greatest concordance rate of 95.7% (95% confidence limit, 85.2%-99.5%) observed for pT1 tumors., Conclusion: Ultrasonography underestimates the tumor size and volume, with the underestimation increasing for larger tumors. Hence, the concordance rate in tumor size stage between ultrasonography and pathology is tumor size dependent, with the greatest concordance rate observed for pT1 tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Methylglyoxal (MG) is a predominant precursor for advanced glycation end products (AGEs) due to its protein glycation reactions, which are the major causes of diabetic complications. MG is explored as a significant biomarker towards the prediction of diabetic complications. With this background, a non-enzymatic electrochemical biosensor has been developed to detect MG in human blood plasma samples. Microwave synthesized V 2 O 5 nanoplates were used as interface material in the fabrication of modified gold (Au) working electrode for electrochemical MG biosensor. Orthorhombic crystal structured V 2 O 5 with an oxidation state of +5 exhibited specific MG sensing performance. Cyclic voltammetry and amperometry studies confirmed the electrocatalytic nature of V 2 O 5 nanoplates modified Au electrode in the detection of MG. Non-enzymatic V 2 O 5 modified Au electrode showed a sensitivity of 4.519µAµM -1 with a linear range of 3-30µM, limit of detection (LOD) of 0.24µM, limit of quantification (LOQ) of 0.80µM and a response time less than 8s towards MG. The lifetime and percentage recovery of the sensor was found to be 25 days (90%) and 102.5-108.7% respectively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Dedicated breast computed tomography (CT) is the latest in a long history of breast imaging techniques dating back to the 1960s. Breast imaging is performed both for cancer screening as well as for diagnostic evaluation of symptomatic patients. Dedicated breast CT received US Food and Drug Administration approval for diagnostic use in 2015 and is slowly gaining recognition for its value in diagnostic 3-dimensional imaging of the breast, and also for injected contrast-enhanced imaging applications. Conventional mammography has known limitations in sensitivity and specificity, especially in dense breasts. Breast tomosynthesis was US Food and Drug Administration approved in 2011 and is now widely used. Dedicated breast CT is the next technological advance, combining real 3-dimensional imaging with the ease of contrast administration. The lack of painful compression and manipulation of the breasts also makes dedicated breast CT much more acceptable for the patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Early detection of breast cancers by mammography in conjunction with adjuvant therapy has contributed to reduction in breast cancer mortality. Mammography remains the "gold-standard" for breast cancer screening but is limited by tissue superposition. Digital breast tomosynthesis and more recently, dedicated breast computed tomography have been developed to alleviate the tissue superposition problem. However, all of these modalities rely upon x-ray attenuation contrast to provide anatomical images, and there are ongoing efforts to develop and clinically translate alternative modalities. These emerging modalities could provide for new contrast mechanisms and may potentially improve lesion detection and diagnosis. In this article, several of these emerging modalities are discussed with a focus on technologies that have advanced to the stage of in vivo clinical evaluation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The authors have requested to withdraw this manuscript from publication because the study was not conducted in full accordance with the relevant institutional IRB protocol. © RSNA, 2018.

Purpose: Dedicated cone beam breast CT (CBBCT) suffers from x-ray scatter contamination. We aim to identify the source of the significant difference between the scatter distributions estimated by two recent methods proposed by our group and to investigate its effect on CBBCT image quality., Method: We recently proposed two novel methods of scatter correction for CBBCT, using a library based (LB) technique and a forward projection (FP) model. Despite similar enhancement on CBBCT image qualities, these two methods obtain very different scatter distributions. We hypothesize that the off-focus radiation (OFR) is the contributor and results in nontrivial signals in x-ray projections, which is ignored in the scatter estimation via the LB method. Experiments using a thin wire test tool are designed to study the effect of OFR on CBBCT spatial resolution by measuring the point spread function (PSF) and the modulation transfer function (MTF). A narrow collimator setting is used to suppress the OFR-induced signals. In addition, "PSFs" and "MTFs" are measured on clinical CBBCT images obtained by the LB and FP methods using small calcifications as point sources. The improvement of spatial resolution achieved by suppressing OFR in the wire experiment as well as in the clinical study is quantified by the improvement ratios of PSFs and spatial frequencies at different MTF values. Our hypothesis that OFR causes the imaging difference between the FP and LB methods is verified if these ratios obtained from experimental and clinical data are consistent., Results: In the wire experiment, the results show that suppression of OFR increases the maximum signal of the PSF by about 14% and reduces the full-width-at-half-maximum (FWHM) by about 12.0%. Similar improvement on spatial resolution is achieved by the FP method compared with the LB method in the patient study. The improvement ratios of spatial frequencies at different MTF values without OFR match very well in both studies at a level of around 16%, with an average root-mean-square difference of 0.47%., Conclusion: The results of the wire experiment and the clinical study indicate that the main difference between the LB and FP methods is whether the OFR-induced signals are included after scatter correction. Our study further shows that OFR significantly affects the image spatial resolution of CBBCT, indicating that the visualization of micro-calcifications is susceptible to OFR contamination. Our finding is therefore important in further improvement of diagnostic performance of CBBCT., (© 2017 American Association of Physicists in Medicine.)

Increased consumption of fried foods such as grilled chicken contains elevated levels of methylglyoxal (MG), which is associated with diabetes mellitus. Hence, in this work, glyoxalase 1(GLO 1) based, zinc oxide (ZnO) flakes interfaced mediator free electrochemical biosensor was developed to detect MG in grilled chicken. ZnO flakes were synthesized by direct precipitation method. X-ray diffractometer and field emission scanning electron microscope were used to study the structural and morphological characteristics of ZnO flakes. The immobilization of GLO 1 on Pt/ZnO flakes modified electrode was confirmed by Fourier transform infrared spectroscopy. Cyclic voltammetric and amperometric studies were carried out using Pt/ZnO flakes/GLO 1 working electrode. The developed biosensor exhibited linear range of 0.6-2.0 µM, sensitivity of 0.281 µA µM -1 , LOD of 9 nM with a response time of <4 s and shelf life of 18 days (89%).

Background and Purpose: The standard head CT protocol makes detection of a temporal bone fracture difficult. The purposes of our study are to revisit the finding of air in various locations around the temporal bone as an indirect sign of fracture and determine if findings could predict fracture pattern., Materials and Methods: We searched the radiology reports for the keyword "temporal bone fracture." We recorded the presence of air in multiple locations around the temporal bone and pneumocephalus, opacification of the mastoid air cells or the middle ear cavity, and dominant fracture pattern. Statistical analyses were performed using statistical software., Results: A total of 135 patients (mean age 40 ± 20.1 years, 101 male, 34 female, range 1-91) had 152 fractures. At least one indirect finding was present in 143 (94.1%) fractures. Air was present adjacent to the styloid process in 94 (61.8%), in the temporomandibular joint in 80 (52.6%), adjacent to the mastoid process in 57 (37.5%), and along the adjacent dural venous sinus in 33 (21.7%) fractures. Mastoid opacification was present in 139 (91.4%) fractures. Opacification of the middle ear cavity was present in 121 (79.6%) fractures. A complex fracture significantly and positively correlated with pneumocephalus., Conclusion: In the setting of trauma, air around the temporal bone and opacification of the mastoid air cells or middle ear cavity should prompt consideration of a temporal bone fracture even if the fracture line is not visible. The presence of pneumocephalus predicts a higher chance of complex fracture pattern.

Background: Vascular remodeling in response to implantation of a tissue engineering scaffold such as a flow diverter (FD) leads to the cure of intracranial aneurysms. We hypothesize that the vascular response is dependent on FD design, and CD34+ progenitor cells play an important role in the endothelialization of the implant., Methods: Sixteen rabbit aneurysms were randomly treated with two different single-layer braided FDs made of cobalt-chrome alloys. The FD-48 and FD-72 devices had 48 and 72 wires, respectively. Aneurysm occlusion rate was assessed during the final digital subtraction angiogram at 10, 20, 30, and 60 days (n=2 per device per time point). Implanted vessels were analyzed with scanning electron microscopy for tissue coverage, endothelialization, and immuno-gold labeling for CD34+ cells., Results: Complete aneurysm occlusion rates were similar between the devices; however, complete or near complete occlusion was more frequently observed in aneurysms with neck ≤4.2 mm (p=0.008). Total tissue coverage at 10 days over the surface of the FD-48 and FD-72 devices was 56.4±11.6% and 76.6±3.6%, respectively. Endothelial cell growth over the surface was time-dependent for the FD-72 device (Spearman's r=0.86, p=0.013) but not for the FD-48 device (Spearman's r=-0.59, p=0.094). The endothelialization score was marginally correlated with the distance from the aneurysm neck for the FD-48 device (Spearman's r=1, p=0.083) but not for the FD-72 device (Spearman's r=0.8, p=0.33). CD34+ cells were present along the entirety of both devices at all time points., Conclusions: This study gives preliminary evidence that temporal and spatial endothelialization is dependent on FD design. Circulating CD34+ progenitor cells contribute to endothelialization throughout the healing process., Competing Interests: Competing interests: MJG has been a consultant on a fee-per-hour basis for Codman Neurovascular and Stryker Neurovascular; holds stock in InNeuroCo; and has received research support from the National Institutes of Health (NIH), Codman Neurovascular, Stryker Neurovascular, Microvention, Medtronic Neurovascular, Philips Healthcare, InNeuroCo, Neuronal Protection Systems, the Wyss Institute and Silk Road. ASP has received research grants from Medtronic Neurovascular and Stryker Neurovascular. AKW: Consultant for Codman Neurovascular and Stryker Neurovascular; research grant: NIH, Philips Healthcare, Wyss Institute; speaker: Harvard Postgraduate Course, Miami Cardiovascular Institute; co-founder of InNeuroCo and major stockholder; stocks in EpiEB and Pulsar Medical. IS: Consultant for Stryker Neurovascular and ev3/ Covidien, Chestnut Medical. JA and SL are employed by Stryker Neurovascular., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Rationale and Objectives: Evaluation of nodal involvement in early-stage breast cancers (T1 or T2) changed following the Z11 trial; however, not all patients meet the Z11 inclusion criteria. Hence, the relevance of ultrasound imaging of the axilla and fine-needle aspiration biopsy (FNA) in early-stage breast cancers was investigated., Materials and Methods: In this single-center, retrospective study, 758 subjects had pathology-verified breast cancer diagnosis over a 3-year period, of which 128 subjects with T1 or T2 breast tumors had abnormal axillary lymph nodes on ultrasound, had FNA, and proceeded to axillary surgery. Ultrasound images were reviewed and analyzed using multivariable logistic regression to identify the features predictive of positive FNA. Accuracy of FNA was quantified as the area under the receiver operating characteristic curve with axillary surgery as reference standard., Results: Of 128 subjects, 61 were positive on FNA and 65 were positive on axillary surgery. Sensitivity, specificity, positive predictive value, and negative predictive value of FNA were 52 of 65 (80%), 54 of 63 (85.7%), 52 of 61(85.2%), and 54 of 67 (80.5%), respectively. After adjusting for neoadjuvant chemotherapy between FNA and surgery, a positive FNA was associated with higher likelihood for positive axillary surgery (odds ratio: 22.7; 95% confidence interval [CI]: 7.2-71.3, P < .0001), and the accuracy of FNA was 0.801 (95% CI: 0.727-0.876). Among ultrasound imaging features, cortical thickness and abnormal hilum were predictive (P < .017) of positive FNA with accuracy of 0.817 (95% CI: 0.741-0.893)., Conclusions: Ultrasound imaging and FNA can play an important role in the management of early breast cancers even in the post-Z11 era. Higher weightage can be accorded to cortical thickness and hilum during ultrasound evaluation., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Acetylation of proteins as a post-translational modification is gaining rapid acceptance as a cellular control mechanism on par with other protein modification mechanisms such as phosphorylation and ubiquitination. Through genetic manipulations and evolving proteomic technologies, identification and consequences of transcription factor acetylation is beginning to emerge. In this review, we summarize the field and discuss newly unfolding mechanisms and consequences of transcription factor acetylation in normal and stressed hearts. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions.

Background and Purpose: The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement., Methods: A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy., Results: Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001)., Conclusions: A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy., (© 2015 American Heart Association, Inc.)

Background: Rates of durable aneurysm occlusion following coil embolization vary widely, and a better understanding of coil mass mechanics is desired. The goal of this study is to evaluate the impact of packing density and coil uniformity on aneurysm permeability., Methods: Aneurysm models were coiled using either Guglielmi detachable coils or Target coils. The permeability was assessed by taking the ratio of microspheres passing through the coil mass to those in the working fluid. Aneurysms containing coil masses were sectioned for image analysis to determine surface area fraction and coil uniformity., Results: All aneurysms were coiled to a packing density of at least 27%. Packing density, surface area fraction of the dome and neck, and uniformity of the dome were significantly correlated (p<0.05). Hence, multivariate principal components-based partial least squares regression models were used to predict permeability. Similar loading vectors were obtained for packing and uniformity measures. Coil mass permeability was modeled better with the inclusion of packing and uniformity measures of the dome (r(2)=0.73) than with packing density alone (r(2)=0.45). The analysis indicates the importance of including a uniformity measure for coil distribution in the dome along with packing measures., Conclusions: A densely packed aneurysm with a high degree of coil mass uniformity will reduce permeability., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To analyze the effect of lobe selection, needle gauge, and number of passes on procedure outcomes in terms of specimen length and post-procedure complications., Methods: In this HIPAA-compliant, IRB-approved retrospective study, the data from 771 ultrasound-guided adult parenchymal liver biopsies were analyzed. Post-procedure complications were assigned a 3-point rating scale. Associations between specimen length and post-procedure complications with lobe laterality, needle gauge, and number of passes were analyzed. Multivariate logistic regression models were used to analyze the likelihood for achieving a specimen length of at least 2 cm., Results: Post-procedure complications were not associated with lobe laterality, needle gauge, and number of passes (p > 0.3). Specimen length was associated with the number of passes dichotomized at the study mean (p = 0.007), but not with lobe laterality or needle gauge (p > 0.2). After adjusting for lobe laterality and needle gauge, procedures with 1 or 2 passes were associated with a higher likelihood of obtaining a 2 cm or longer specimen (OR 2.469; CI 1.08-5.63, p = 0.0315) than procedures with 3 or more passes, possibly due to poorer sample quality. After adjusting for lobe laterality, an 18-gauge needle was associated with higher odds of a biopsy procedure with 1 or 2 passes (OR 3.665; CI 1.93-6.95, p < 0.0001) than a 20-gauge needle., Conclusions: Lobe laterality was not associated with specimen length or post-procedure complications. An 18-gauge needle compared to a 20-gauge needle could reduce the need for a procedure with more than 2 passes. There was no difference in post-procedure complications between the two needle sizes.

Objectives: In this prospective pilot study, the feasibility of non-contrast dedicated breast computed tomography (bCT) to determine primary tumor volume and monitor its changes during neoadjuvant chemotherapy (NAC) treatment was investigated., Materials and Methods: Eleven women who underwent NAC were imaged with a clinical prototype dedicated bCT system at three time points - pre-, mid-, and post-treatment. The study radiologist marked the boundary of the primary tumor from which the tumor volume was quantified. An automated algorithm was developed to quantify the primary tumor volume for comparison with radiologist's segmentation. The correlation between pre-treatment tumor volumes from bCT and MRI, and the correlation and concordance in tumor size between post-treatment bCT and pathology were determined., Results: Tumor volumes from automated and radiologist's segmentations were correlated (Pearson's r = 0.935, P < 0.001) and were not different over all time points [P = 0.808, repeated measures analysis of variance (ANOVA)]. Pre-treatment tumor volumes from MRI and bCT were correlated (r = 0.905, P < 0.001). Tumor size from post-treatment bCT was correlated with pathology (r = 0.987, P = 0.002) for invasive ductal carcinoma larger than 5 mm and the maximum difference in tumor size was 0.57 cm. The presence of biopsy clip (3 mm) limited the ability to accurately measure tumors smaller than 5 mm. All study participants were pathologically assessed to be responders, with three subjects experiencing complete pathologic response for invasive cancer and the reminder experiencing partial response. Compared to pre-treatment tumor volume, there was a statistically significant (P = 0.0003, paired t-test) reduction in tumor volume at mid-treatment observed with bCT, with an average tumor volume reduction of 47%., Conclusions: This pilot study suggests that dedicated non-contrast bCT has the potential to serve as an expedient imaging tool for monitoring tumor volume changes during NAC. Larger studies are needed in future.

Background and Purpose: Noninvasive imaging identifying a predictive biomarker of the bleeding risk of unruptured intracranial aneurysms (UIAs) is needed. We investigated a potential biomarker of UIA instability, myeloperoxidase, in human aneurysm tissue., Methods: Human brain aneurysms were harvested after clipping and were histologically and biochemically evaluated for the presence of myeloperoxidase. Of the tissue collected, 3 were from ruptured aneurysms and 20 were from UIAs. For each UIA, its 5-year aneurysm rupture risk was determined using the Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm and Site of Aneurysm (PHASES) model., Results: All ruptured aneurysms were myeloperoxidase positive. Of the UIAs, half were myeloperoxidase positive. The median 5-year aneurysm rupture risk was higher for myeloperoxidase-positive UIA (2.28%) than myeloperoxidase-negative UIA (0.69%), and the distributions were statistically different (P<0.005, Wilcoxon-Mann-Whitney test). The likelihood for myeloperoxidase-positive UIA was significantly associated (P=0.031) with aneurysm rupture risk (odds ratio, 4.79; 95% confidence limits, 1.15-19.96)., Conclusions: Myeloperoxidase is associated with PHASES estimated risk of aneurysm rupture and may potentially be used as an imaging biomarker of aneurysm instability.

Sustained increases in glucose flux via the aldose reductase (AR) pathway have been linked to diabetic vascular complications. Previous studies revealed that glucose flux via AR mediates endothelial dysfunction and leads to lesional hemorrhage in diabetic human AR (hAR) expressing mice in an apoE(-/-) background. Our studies revealed sustained activation of Egr-1 with subsequent induction of its downstream target genes tissue factor (TF) and vascular cell adhesion molecule-1 (VCAM-1) in diabetic apoE(-/-)hAR mice aortas and in high glucose-treated primary murine aortic endothelial cells expressing hAR. Furthermore, we observed that flux via AR impaired NAD(+) homeostasis and reduced activity of NAD(+)-dependent deacetylase Sirt-1 leading to acetylation and prolonged expression of Egr-1 in hyperglycemic conditions. In conclusion, our data demonstrate a novel mechanism by which glucose flux via AR triggers activation, acetylation, and prolonged expression of Egr-1 leading to proinflammatory and prothrombotic responses in diabetic atherosclerosis.

In extensive liver resection secondary to primary or metastatic liver tumors, or in living donor liver transplantation, strategies to quell deleterious inflammatory responses and facilitate regeneration are essential. The receptor for advanced glycation endproducts (RAGE) and myeloid differentiating factor 88 (Myd88) are implicated in the inflammatory response. To establish the contributions of RAGE vs. Myd88 signaling in extensive liver resection, we probed the effect of RAGE and/or Myd88, the latter primarily a key transducer of major toll-like receptors and also implicated in interleukin-1 (Il1) signaling, in a murine model of extensive (85%) hepatectomy. We report that, although Myd88 is thoroughly essential for survival via regulation of NF-κB and TNF-α, deletion of RAGE significantly improved survival compared to wild-type, Myd88-null, or RAGE-null/Myd88-null mice. RAGE opposes Myd88 signaling at multiple levels: by suppression of p65 levels, thereby reducing activation of NF-κB and consequent production of cyclin D1, and by suppression of Il6-mediated phosphorylation of Stat3, thereby down-regulating Pim1 and suppressing the hyperplastic response. Further, RAGE-dependent suppression of glyoxalase1, a detoxification pathway for pre-AGEs, enhances AGE levels and suppresses Il6 action. We conclude that blockade of RAGE may rescue liver remnants from the multiple signals that preclude adaptive proliferation triggered primarily by Myd88 signaling pathways.

Digital breast tomosynthesis (DBT) is a limited-angle tomographic x-ray imaging technique that reduces the effect of tissue superposition observed in planar mammography. An integrated imaging platform that combines DBT with near infrared spectroscopy (NIRS) to provide co-registered anatomical and functional imaging is under development. Incorporation of anatomic priors can benefit NIRS reconstruction. In this work, we provide a segmentation and classification method to extract potential lesions, as well as adipose, fibroglandular, muscle and skin tissue in reconstructed DBT images that serve as anatomic priors during NIRS reconstruction. The method may also be adaptable for estimating tumor volume, breast glandular content, and for extracting lesion features for potential application to computer aided detection and diagnosis.

In this paper, the performance of an 8 cm x 8 cm three-side buttable charge-coupled device (CCD)-based imager specially designed for high-resolution fluoroscopy and operating in fluoroscopic (30 frames/second) mode is presented in terms of the presampling modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE). The 8 cm x 8 cm CCD imager is coupled to a 450 microm thick CsI:Tl scintillator by nondemagnifying (straight, 1:1) fiberoptics. The CCD imager has a fundamental pixel pitch of 39 microm and incorporates an optically opaque interline (data) channel. The CCD imager was operated at 156 microm pixel pitch by binning 4 x 4 adjacent pixels prior to readout. The fluoroscopic image lag was measured and accounted for in the DQE estimate to provide lag-corrected DQE. The measured limiting spatial resolution at 10% presampling MTF with the imager operated at 156 microm pixel pitch (Nyquist sampling limit: 3.21 cy/mm) was 3.6 cy/mm. In the pulsed fluoroscopic mode, the first-frame image lag was less than 0.9%. The lag-corrected DQE(0) of approximately 0.62 was achieved even at a low fluoroscopic exposure rate of 1 microR/frame. Grid phantom measurements indicate no appreciable distortion. Results from DQE and image lag measurements at fluoroscopic exposure rates combined with the high spatial resolution observed from the MTF suggest that this type of imager or its variants may be a potential candidate for high-resolution neuro-interventional imaging, cardiovascular imaging, pediatric angiography, and small animal imaging. Since the CCD is three-side buttable, four such CCD modules can be joined to form a 2 x 2 matrix providing a field of view of 16 cm x 16 cm.

Cascaded linear systems based modeling techniques have been used in the past to predict important system parameters that have a direct impact on image quality. Such models are also useful in optimizing system parameters to improve image quality. In this work, detailed analysis of a solid-state fluoroscopic imaging system intended for high-resolution angiography is presented with the use of such a model. The imaging system analyzed through this model uses four 8 x 8 cm three-side buttable interlined charge-coupled devices (CCDs) specifically designed for high-resolution angiography and tiled in a seamless fashion to achieve a field of view (FOV) of 16 x 16 cm. Larger FOVs can be achieved by tiling more CCDs in a similar manner. The system employs a CsI:Tl scintillator coupled to the CCDs by straight (nontapering) fiberoptics and can potentially be operated in 78, 156, or 234 microm pixel pitch modes. The system parameters analyzed through this model include presampling modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE). The results of the simulations performed indicate that DQE(0) in excess of 0.6 is achievable, with the imager operating at 156 microm pixel pitch, 30 frames/s, and employing a 450-microm-thick CsI:Tl scintillator, even at a low fluoroscopic exposure rate of 1 microR/frame. Further, at a nominal fluoroscopic exposure rate of 2.5 microR/frame there was no noticeable degradation of the DQE even at the 78 microm pixel pitch mode suggesting that it is feasible to perform high-resolution angiography hitherto unattainable in clinical practice.

In this investigation the effect of JPEG 2000 compression on the contrast-detail (CD) characteristics of digital mammography images was studied using an alternative forced choice (AFC) technique. Images of a contrast-detail phantom, acquired using a clinical full-field digital mammography system, were compressed using a commercially available software product (JPEG 2000). Data compression was achieved at ratios of 1:1, 10:1, 20:1, and 30:1 and the images were reviewed by seven observers on a high-resolution display. Psychophysical detection characteristics were first computed by fitting perception data using a maximum-likelihood technique from which CD curves were derived at 50%, 62.5%, and 75% threshold levels. Statistical analysis indicated no significant difference in the perception of mean disk thickness up to 20:1 compression except for disk diameter of 1 mm. All other compression combinations exhibited significant degradation in CD characteristics.