miR-223-3p Prevents Necroptotic Macrophage Death by Targeting Ripk3 in a Negative Feedback Loop and Consequently Ameliorates Advanced Atherosclerosis.

BACKGROUND: The formation of large necrotic cores results in vulnerable atherosclerotic plaques, which can lead to severe cardiovascular diseases. However, the specific regulatory mechanisms underlying the development of necrotic cores remain unclear. METHODS: To evaluate how the modes of lesional cell death are reprogrammed during the development of atherosclerosis, the expression levels of key proteins that are involved in the necroptotic, apoptotic, and pyroptotic pathways were compared between different stages of plaques in humans and mice. Luciferase assays and loss-of-function studies were performed to identify the microRNA-mediated regulatory mechanism that protects foamy macrophages from necroptotic cell death. The role of this mechanism in atherosclerosis was determined by using a knockout mouse model with perivascular drug administration and tail vein injection of microRNA inhibitors in Apoe-/- mice. RESULTS: Here, we demonstrate that the necroptotic, rather than the apoptotic or pyroptotic, pathway is more activated in advanced unstable plaques compared with stable plaques in both humans and mice, which closely correlates with necrotic core formation. The upregulated expression of Ripk3 (receptor-interacting protein kinase 3) promotes the C/EBPß (CCAAT/enhancer binding protein beta)-dependent transcription of the microRNA miR-223-3p, which conversely inhibits Ripk3 expression and forms a negative feedback loop to regulate the necroptosis of foamy macrophages. The knockout of the Mir223 gene in bone marrow cells accelerates atherosclerosis in Apoe-/- mice, but this effect can be rescued by Ripk3 deficiency or treatment with the necroptosis inhibitors necrostatin-1 and GSK-872. Like the Mir223 knockout, treating Apoe-/- mice with miR-223-3p inhibitors increases atherosclerosis. CONCLUSIONS: Our study suggests that miR-223-3p expression in macrophages protects against atherosclerotic plaque rupture by limiting the formation of necrotic cores, thus providing a potential microRNA therapeutic candidate for atherosclerosis.

Theoretical and experimental evaluation of multi-band EPI for high-resolution whole brain pCASL Imaging.

Multi-band echo planar imaging (MB-EPI), a new approach to increase data acquisition efficiency and/or temporal resolution, has the potential to overcome critical limitations of standard acquisition strategies for obtaining high-resolution whole brain perfusion imaging using arterial spin labeling (ASL). However, the use of MB also introduces confounding effects, such as spatially varying amplified thermal noise and leakage contamination, which have not been evaluated to date as to their effect on cerebral blood flow (CBF) estimation. In this study, both the potential benefits and confounding effects of MB-EPI were systematically evaluated through both simulation and experimentally using a pseudo-continuous arterial spin labeling (pCASL) strategy. These studies revealed that the amplified noise, given by the geometry factor (g-factor), and the leakage contamination, assessed by the total leakage factor (TLF), have a minimal impact on CBF estimation. Furthermore, it is demonstrated that MB-EPI greatly benefits high-resolution whole brain pCASL studies in terms of improved spatial and temporal signal-to-noise ratio efficiencies, and increases compliance with the assumptions of the commonly used single blood compartment model, resulting in improved CBF estimates.

Comparison of RF body coils for MRI at 3 T: a simulation study using parallel transmission on various anatomical targets.

The performance of multichannel transmit coil layouts and parallel transmission (pTx) RF pulse design was evaluated with respect to transmit B1 (B1 (+)) homogeneity and specific absorption rate (SAR) at 3 T for a whole body coil. Five specific coils were modeled and compared: a 32-rung birdcage body coil (driven either in a fixed quadrature mode or a two-channel transmit mode), two single-ring stripline arrays (with either 8 or 16 elements), and two multi-ring stripline arrays (with two or three identical rings, stacked in the z axis and each comprising eight azimuthally distributed elements). Three anatomical targets were considered, each defined by a 3D volume representative of a meaningful region of interest (ROI) in routine clinical applications. For a given anatomical target, global or local SAR controlled pTx pulses were designed to homogenize RF excitation within the ROI. At the B1 (+) homogeneity achieved by the quadrature driven birdcage design, pTx pulses with multichannel transmit coils achieved up to about eightfold reduction in local and global SAR. When used for imaging head and cervical spine or imaging thoracic spine, the double-ring array outperformed all coils, including the single-ring arrays. While the advantage of the double-ring array became much less pronounced for pelvic imaging, with a substantially larger ROI, the pTx approach still provided significant gains over the quadrature birdcage coil. For all design scenarios, using the three-ring array did not necessarily improve the RF performance. Our results suggest that pTx pulses with multichannel transmit coils can reduce local and global SAR substantially for body coils while attaining improved B1 (+) homogeneity, particularly for a "z-stacked" double-ring design with coil elements arranged on two transaxial rings.

Perfusion reduction at transcatheter intraarterial perfusion MR imaging: a promising intraprocedural biomarker to predict transplant-free survival during chemoembolization of hepatocellular carcinoma.

PURPOSE: To investigate the predictive value of transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging-measured tumor perfusion changes during transarterial chemoembolization on transplant-free survival (TFS) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all patients. Fifty-one consecutive adult patients with surgically unresectable single or multifocal measurable HCC and adequate laboratory parameters who underwent chemoembolization in a combined MR imaging-interventional radiology suite between February 2006 and June 2010 were studied. Tumor perfusion changes during chemoembolization were measured by using TRIP MR imaging with area under the time-signal intensity curve calculation. The end point of the study was TFS. The authors assessed the correlation between the percentage perfusion reduction in the tumor during chemoembolization and TFS by using univariate and multivariate analyses. RESULTS: Fifty patients (mean age, 61 years; 39 men aged 42-87 years [mean age, 61 years] and 11 women aged 49-83 years [mean age, 62 years]) were eligible for the analysis. Patients with 35%-85% intraprocedural tumor area under the time-signal intensity curve reduction (n = 32) showed significantly improved median TFS compared with patients with an area under the time-signal intensity curve reduction outside this range (n = 18) (16.6 months [95% confidence interval: 11.2, 22.0 months] vs 9.3 months [95% confidence interval: 6.6, 12.0 months], respectively; P = .046; hazard ratio: 0.46; 95% confidence interval: 0.21, 1.00). The cumulative TFS rates in the 35%-85% and less than 35% or more than 85% perfusion reduction groups at 1, 2, and 5 years after chemoembolization were 66.4%, 42.2%, and 28.2% versus 33.8%, 16.9%, and 0%, respectively. CONCLUSION: The study shows evidence of an association between intraprocedural tumor perfusion reduction during chemoembolization and TFS and suggests the utility of TRIP MR imaging- measured tumor perfusion reduction as an intraprocedural imaging biomarker during chemoembolization.

Ecotoxicological impact of naproxen on Eisenia fetida: Unraveling soil contamination risks and the modulating role of microplastics.

Soils represent crucial sinks for pharmaceuticals and microplastics, making them hotspots for pharmaceuticals and plastic pollution. Despite extensive research on the toxicity of pharmaceuticals and microplastics individually, there is limited understanding of their combined effects on soil biota. This study focused on the earthworm Eisenia fetida as test organism to evaluate the biotoxicity and bioaccumulation of the typical pharmaceutical naproxen and microplastics in earthworms. Results demonstrated that high concentrations of naproxen (100 mg kg-1) significantly increased the malondialdehyde (MDA) content, inducing lipid peroxidation. Even though the low exposure of naproxen exhibits no significant influence to Eisenia fetida, the lipid peroxidation caused by higher concentration than environmental relevant concentrations necessitate attention due to temporal and spatial concentration variability found in the soil environment. Meanwhile, microplastics caused oxidative damage to antioxidant enzymes by reducing the superoxide dismutase (SOD) activity and MDA content in earthworms. Metabolome analysis revealed increased lipid metabolism in naproxen-treated group and reduced lipid metabolism in the microplastic-treated group. The co-exposure of naproxen and microplastics exhibited a similar changing trend to the microplastics-treated group, emphasizing the significant influence of microplastics. The detection of numerous including lipids like 17-Hydroxyandrostane-3-glucuronide, lubiprostone, morroniside, and phosphorylcholine, serves to identify potential biomarkers for naproxen and microplastics exposure. Additionally, microplastics increased the concentration of naproxen in earthworms at sub-organ and subcellular level. This study contributes valuable insights into the biotoxicity and distribution of naproxen and microplastics in earthworms, enhancing our understanding of their combined ecological risk to soil biota.

Peptidyl-prolyl isomerase F as a prognostic biomarker associated with immune infiltrates and mitophagy in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide, with unfavorable treatment outcomes. Peptidyl-prolyl isomerase F (PPIF) is known to influence the malignancy traits of tumor progression by modulating the bioenergetics and mitochondrial permeability in cancer cells; however, its role in LUAD remains unclear. Our study seeks to investigate the clinical significance, tumor proliferation, and immune regulatory functions of PPIF in LUAD. Methods: The expression of PPIF in LUAD tissues and cells was assessed using bioinformatics analysis, immunohistochemistry (IHC), and Western blotting. Survival curve analysis was conducted to examine the prognostic association between PPIF expression and LUAD. The immunomodulatory role of PPIF in LUAD was assessed through the analysis of PPIF expression and immune cell infiltration. A series of gain- and loss-of-function experiments were conducted on PPIF to investigate its biological functions in LUAD both in vitro and in vivo. The mechanisms underlying PPIF's effects on LUAD were delineated through functional enrichment analysis and Western blotting assays. Results: PPIF exhibited overexpression in LUAD tissues compared to normal controls. Survival curve analysis revealed that patients with LUAD exhibiting higher PPIF expression demonstrated decreased overall survival and a shorter progression-free interval. PPIF was implicated in modulating immune cell infiltration, particularly in regulating the T helper 1-T helper 2 cell balance. Functionally, PPIF was discovered to promote tumor cell proliferation and advance cell-cycle progression. Furthermore, PPIF could impede mitophagy by targeting the FOXO3a/PINK1-Parkin signaling pathway. Conclusions: The findings of this study indicate that the prognosis-related gene PPIF may have a significant role in the regulation of LUAD cell proliferation, tumor-associated immune cell infiltration, and mitophagy, and thus PPIF may be a promising therapeutic target of LUAD.

Pushing spatial and temporal resolution for functional and diffusion MRI in the Human Connectome Project.

The Human Connectome Project (HCP) relies primarily on three complementary magnetic resonance (MR) methods. These are: 1) resting state functional MR imaging (rfMRI) which uses correlations in the temporal fluctuations in an fMRI time series to deduce 'functional connectivity'; 2) diffusion imaging (dMRI), which provides the input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture; and 3) task based fMRI (tfMRI), which is employed to identify functional parcellation in the human brain in order to assist analyses of data obtained with the first two methods. We describe technical improvements and optimization of these methods as well as instrumental choices that impact speed of acquisition of fMRI and dMRI images at 3T, leading to whole brain coverage with 2 mm isotropic resolution in 0.7 s for fMRI, and 1.25 mm isotropic resolution dMRI data for tractography analysis with three-fold reduction in total dMRI data acquisition time. Ongoing technical developments and optimization for acquisition of similar data at 7 T magnetic field are also presented, targeting higher spatial resolution, enhanced specificity of functional imaging signals, mitigation of the inhomogeneous radio frequency (RF) fields, and reduced power deposition. Results demonstrate that overall, these approaches represent a significant advance in MR imaging of the human brain to investigate brain function and structure.

Cardiac imaging at 7 Tesla: Single- and two-spoke radiofrequency pulse design with 16-channel parallel excitation.

PURPOSE: Higher signal to noise ratio (SNR) and improved contrast have been demonstrated at ultra-high magnetic fields (≥7 Tesla [T]) in multiple targets, often with multi-channel transmit methods to address the deleterious impact on tissue contrast due to spatial variations in B1 (+) profiles. When imaging the heart at 7T, however, respiratory and cardiac motion, as well as B0 inhomogeneity, greatly increase the methodological challenge. In this study we compare two-spoke parallel transmit (pTX) RF pulses with static B1 (+) shimming in cardiac imaging at 7T. METHODS: Using a 16-channel pTX system, slice-selective two-spoke pTX pulses and static B1 (+) shimming were applied in cardiac CINE imaging. B1 (+) and B0 mapping required modified cardiac triggered sequences. Excitation homogeneity and RF energy were compared in different imaging orientations. RESULTS: Two-spoke pulses provide higher excitation homogeneity than B1 (+) shimming, especially in the more challenging posterior region of the heart. The peak value of channel-wise RF energy was reduced, allowing for a higher flip angle, hence increased tissue contrast. Image quality with two-spoke excitation proved to be stable throughout the entire cardiac cycle. CONCLUSION: Two-spoke pTX excitation has been successfully demonstrated in the human heart at 7T, with improved image quality and reduced RF pulse energy when compared with B1 (+) shimming.

Bioaccumulation, internal distribution and toxicity of bisphenol S in the earthworm Eisenia fetida.

Due to the strict rules and restrictions on the utilization of bisphenol A (BPA) around the world, an emerging endocrine disrupting chemical, bisphenol S (BPS) has been widely utilized as a substitute and frequently detected in the environment, even in the human body. Although it has been widely studied in the aquatic systems, the fate and toxicological effect of BPS in soil invertebrates are poorly known. This study presented a comprehensive exploration into the attenuation, bioaccumulation, and physiological distribution of BPS in an ecologically significant soil invertebrate, as well as its subsequent ecotoxicological effect to earthworm for the first time. The E. fetida could promote the BPS attenuation in soil, with degradation rates of 92.8 ± 1.6 % and 98.6 ± 1.1 % at dosage of 1.0 mg/kg dry weight soil (DWS) and 0.1 mg/kg DWS, respectively. The bioaccumulation of BPS in the earthworm was up to 111.6 ± 6.0 mg/kg lipid and 12.9 ± 2.9 mg/kg lipid with the initial dosage of 1.0 mg/kg DWS and 0.1 mg/kg DWS, respectively. Furthermore, BPS could induce oxidative stress and the process of antioxidant defense in earthworm cells at relatively high dose (1.0 mg/kg DWS and 10.0 mg/kg DWS), suggesting potential risks of BPS to the soil environment. This study could contribute to a more in-depth understanding of the fate of BPS in soil-earthworm system, and indicate a necessity for better understanding the environmental fate and ecological risks of BPA substitutes in the future.

Locoregional chemoembolic delivery: prediction with transcatheter intraarterial perfusion MRI.

OBJECTIVE: To our knowledge there is currently no quantitative preprocedural method for predicting the distribution and selectivity of delivery of chemoembolic material during trans-arterial chemoembolization. Transcatheter intraarterial perfusion MRI has been developed as a method of quantifying hepatic arterial perfusion. The purpose of this study was to investigate whether findings at transcatheter intraarterial perfusion MRI before chemoembolization can be used to predict uptake of the chemoembolic material delivered during chemoembolization. SUBJECTS AND METHODS: We compared quantitative prechemoembolization transcatheter intraarterial perfusion MRI parameters with analogous postchemoembolization CT chemoembolic distribution parameters and analyzed correlation using the Pearson correlation coefficient. These MRI and CT parameters included volume of distribution (a metric for volumetric liver perfusion or therapeutic agent delivery) and chemoembolic delivery selectivity factor (a ratio of volume-normalized tumor to background signal intensity that indicates the selectivity of chemoembolic delivery). RESULTS: Twenty-four hepatocellular carcinomas were targeted in 18 patients (14 men, four women; mean age, 66 years), and segmental or lobar chemoembolization with intraprocedural transcatheter intraarterial perfusion MRI was successful in all 18. Transcatheter intraarterial perfusion MRI and CT volume of distribution did not differ significantly (MRI, 233 cm(3); CT, 235 cm(3); p = 0.857). Transcatheter intraarterial perfusion MRI selectivity factor was an underestimate of CT selectivity factor (MRI, 0.20; CT, 0.25; p = 0.005). Prechemoembolization transcatheter intraarterial perfusion MRI and postchemoembolization CT volume of distribution (r = 0.93; p < 0.001) and selectivity factor (r = 0.95; p < 0.001) showed significant correlation. CONCLUSION: Tumor perfusion measured with transcatheter intraarterial perfusion MRI is predictive of uptake of chemoembolic material before delivery. This MRI technique may have utility as a method of quantifying delivery of the therapeutic agent during chemoembolization and, potentially, other liver-directed locoregional therapies.

Pan-cancer analysis reveals NAA50 as a cancer prognosis and immune infiltration-related biomarker.

Background: N-Alpha-Acetyltransferase 50 (NAA50) has acetyltransferase activity and is important for chromosome segregation. However, the function and mechanism of NAA50 expression in cancer development was still unclear. Here, we systematically researched the function and mechanism of NAA50 in pan-cancer, and further verified the results of NAA50 in lung adenocarcinoma (LUAD). Methods: In this study, using the online databases TIMER2.0, SangerBox3.0, HPA, UCSC, GEPIA, cBioPortal, UALCAN, TISIDB, CancerSEA and LinkedOmics, we focused on the relevance between NAA50 and oncogenesis, progression, methylation, immune infiltration, function and prognosis. In addition, the proliferation of cells was detected by CCK-8 and Edu assay. Finally, we analyzed the relationship between the expression of NAA50 and cell cycle related proteins. Results: Pan-cancer analysis indicated that NAA50 was overexpressed in most cancers. And there was a significant correlation between NAA50 expression and the prognosis of cancer patients. In the meantime, NAA50 gene changes occur in a variety of tumors. Compared with normal tissues, the methylation level of NAA50 promoter increased in most cancer tissues. In addition, the results exhibited that in most cancers, NAA50 was significantly positively correlated with bone myeloid-derived suppressor cell (MDSC) infiltration and negatively correlated with T cell NK infiltration. Moreover, functional enrichment indicated that NAA50 regulates cell cycle and proliferation in LUAD. In vitro experiments testified that knockout of NAA50 could significantly inhibit the proliferation of LUAD. Conclusion: NAA50 may be a potential biomarker and oncogene of pan-cancer, especially LUAD, which may promote the occurrence and development of tumors through different mechanisms. Furthermore, NAA50 was bound up with to immune cell infiltration in pan-cancer, meaning NAA50 may be an important therapeutic target for human cancers.

Four-dimensional transcatheter intraarterial perfusion MRI monitoring of radiofrequency ablation of rabbit VX2 liver tumors.

PURPOSE: To investigate the hypothesis that four-dimensional (4D) transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) can quantify immediate perfusion changes after radiofrequency (RF) ablation in rabbit VX2 liver tumors. MATERIALS AND METHODS: Nine New Zealand White rabbits were used to surgically implant VX2 liver tumors. During ultrasound-guided RF ablation, tumors received either a true or sham ablation. After selective catheterization of the left hepatic artery under x-ray fluoroscopy, we acquired pre- and post-RF ablation 4D TRIP MR images using 3 mL of 2.5% intraarterial gadopentetate dimeglumine. Two regions-of-interest were drawn upon each tumor to generate signal-intensity time curves. Area under the curve (AUC) was calculated to provide semiquantitative perfusion measurements that were compared using a paired t-test (α = 0.05). Ablated tissue was visually confirmed on pathology using Evans blue dye. RESULTS: Mean AUC perfusion of VX2 tumors for the true ablation group decreased by 92.0% (95% confidence interval [CI]: 83.3%-100%), from 1913 (95% CI: 1557, 2269) before RF ablation to 76.6 (95% CI: 18.4, 134.8) after RF ablation (a.u., P < 0.001). Sham-ablated tumors demonstrated no significant perfusion changes. CONCLUSION: 4D TRIP MRI can quantify liver tumor perfusion reductions in VX2 rabbits after RF ablation. This MRI technique can potentially be used to improve tumor response assessment at the time of RF ablation.

Quantitative 4D transcatheter intraarterial perfusion MRI for standardizing angiographic chemoembolization endpoints.

OBJECTIVE: The purpose of this study was to test the hypothesis that subjective angiographic endpoints during transarterial chemoembolization (TACE) of hepatocellular carcinoma are consistent and correlate with objective intraprocedural reductions in tumor perfusion determined with quantitative 4D transcatheter intraarterial perfusion MRI. SUBJECTS AND METHODS: In this prospective study, 18 consecutively registered patients underwent TACE in a combined MRI-interventional radiology suite. Three board-certified interventional radiologists independently graded the angiographic endpoint of each procedure using a previously described subjective angiographic chemoembolization endpoint scale. A consensus endpoint rating was established for each patient. Patients underwent quantitative 4D transcatheter intraarterial perfusion MRI immediately before and after TACE, and mean whole tumor perfusion was calculated from the images. Consistency of subjective angiographic endpoint ratings between observers was evaluated with the intraclass correlation coefficient. The relation between the endpoint ratings and intraprocedural transcatheter intraarterial perfusion MRI changes was evaluated with the Spearman rank correlation coefficient. RESULTS: The subjective angiographic chemoembolization endpoint rating scale showed very good consistency among all observers (intraclass correlation coefficient, 0.80). The consensus endpoint rating correlated significantly with both absolute (r = 0.54, p = 0.022) and percentage (r = 0.85, p < 0.001) reduction in intraprocedural perfusion. CONCLUSION: The subjective angiographic chemoembolization endpoint rating scale shows very good consistency between raters and significantly correlates with objectively measured intraprocedural perfusion reductions during TACE. These results support the use of the scale as a standardized alternative method in quantitative 4D transcatheter intraarterial perfusion MRI to classify patients on the basis of embolic endpoints of TACE.

Chemoembolization endpoints: effect on survival among patients with hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to investigate the relation between angiographic embolic endpoints of transarterial chemoembolization (TACE) and the survival of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was a retrospective assessment of the cases of 105 patients with surgically unresectable HCC who underwent TACE. The cases were classified according to a previously established subjective angiographic chemoembolization endpoint scale. Only one patient had endpoint level I embolization and was excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was used to determine independent prognostic risk factors of survival. RESULTS: The overall median survival period was 21.1 months (95% CI, 15.9-26.4 months). Patients with embolization to subjective angiographic chemoembolization endpoint levels II and III were aggregated and had a significantly longer median survival period (25.6 months; 95% CI, 16.2-35.0 months) than patients with embolization to level IV (17.1 months; 95% CI, 13.3-20.9 months) (p = 0.035). The results of multivariate analysis indicated that all of the following factors were independent negative prognostic indicators of survival: subjective angiographic chemoembolization endpoint level IV (hazard ratio [HR], 2.49; 95% CI, 1.41-4.42; p = 0.002), European Cooperative Oncology Group performance status greater than 0 (HR, 1.97; 95% CI, 1.15-3.37; p = 0.013), American Joint Committee on Cancer stage III or IV (HR, 2.42; 95% CI, 1.27-4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09-3.46; p = 0.025). CONCLUSION: Embolization to an intermediate, substasis endpoint (subjective angiographic chemoembolization endpoint levels II and III) during TACE improves survival compared with embolization to a higher, stasis endpoint (level IV). Interventional oncologists should consider aiming for these intermediate, substasis angiographic endpoints during TACE.

Quantitative 4D transcatheter intraarterial perfusion MRI for monitoring chemoembolization of hepatocellular carcinoma.

PURPOSE: To develop a fully quantitative 4D transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) technique and prospectively test the hypothesis that quantitative 4D TRIP-MRI can be used clinically to monitor intraprocedural liver tumor perfusion reductions during transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: TACE was performed within an x-ray digital subtraction angiography (DSA)-MRI procedure suite in 16 patients with hepatocellular carcinoma. Quantitative 4D TRIP-MRI with targeted radiofrequency field mapping and dynamic longitudinal relaxation rate mapping was used to monitor changes in tumor perfusion during TACE. First-pass perfusion analysis was performed to produce intraprocedural blood flow (Frho) maps. Mean liver tumor perfusions before and after TACE were compared with a paired t-test (alpha = 0.05). RESULTS: Perfusion reductions were successfully measured with quantitative 4D TRIP-MRI in 22 separate tumors during 18 treatment sessions. Mean tumor perfusion Frho decreased from 16.3 (95% confidence interval [CI]: 10.7-21.9) before TACE to 5.0 (95% CI: 3.5-6.5) (mL/min/100 mL) after TACE. Tumor perfusion reductions were statistically significant (P < 0.0005), with a mean absolute perfusion change of 11.4 (95% CI: 5.6-17.1) (mL/min/100 mL) and a mean percentage reduction of 61.0% (95% CI: 48.3%-73.6%). CONCLUSION: Quantitative 4D TRIP-MRI can be successfully performed within clinical interventional settings to monitor intraprocedural changes in liver tumor perfusion during TACE.

Four-dimensional transcatheter intra-arterial perfusion MR imaging before and after uterine artery embolization in the rabbit VX2 tumor model.

PURPOSE: To test the hypothesis that four-dimensional (4D) transcatheter intra-arterial perfusion (TRIP) MR imaging can measure uterine fibroid perfusion changes immediately before and after uterine artery embolization (UAE) in the rabbit VX2 tumor model. MATERIALS AND METHODS: Eight VX2 uterine tumors were grown in six rabbits. After positioning a catheter within the uterine artery, we performed 4D TRIP-MRI measurements with 3-mL injections of 2.5% gadopentetate dimeglumine. We used a dynamic 3D spoiled-gradient echo sequence with in vivo B(1)-field correction for improved accuracy during perfusion quantification. We performed UAE using 1 mL of gelatin microspheres (2 x 10(6) particles; diameter 40-120 mum). Two regions-of-interest were drawn within each tumor upon perfusion maps. Functional embolic endpoints were reported as the mean percent reduction in fibroid tumor perfusion. Measurements before and after UAE were compared using paired t-tests (alpha = 0.05). RESULTS: VX2 uterine tumor perfusion decreased significantly from 27.1 at baseline to 7.09 after UAE (mL/min/100 mL of tissue, P < 0.0001). Overall perfusion reduction was 76.3% (95% confidence interval: 66.3-86.3%). CONCLUSION: Four-dimensional TRIP MRI can objectively quantify uterine fibroid perfusion reductions during UAE in VX2 rabbits. This technique could be used clinically to potentially determine an optimal embolic endpoint with the long-term goals of improving UAE success rates and minimizing procedure-related ischemic pain.

Characterization of kynurenine pathway in patients with diarrhea-predominant irritable bowel syndrome.

Our objectives are to demonstrate whether the kynurenine pathway is activated in diarrhea-type irritable bowel syndrome (IBS-D) patients, and whether the neurotoxic metabolite quinolinic acid (QUIN) is out of balance with the neuroprotective metabolite kynurenic acid (KYNA), and further explore whether this can lead to increase of N-methyl D-aspartate receptor 2B (NMDAR2B) expression in the enteric nervous system and in turn leads to intestinal symptoms and mood disorders. All enrolled healthy controls and patients accepted IBS symptom severity scale (IBS-SSS) score, Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) anxiety and depression scores, and also underwent colonoscopy to collect ileum and colonic mucosa specimens. The expression of NMDAR2B in intestinal mucosa was detected by immunofluorescence, and fasting serum was collected to detect the tryptophan (Trp), kynurenine (KYN), KYNA and QUIN by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Our results showed that the kynurenine pathway of IBS-D patients was activated. The production of QUIN and KYNA was imbalanced and resulting in an increased NMDAR2B for patients with IBS-D, which may be involved in intestinal symptoms and mood disorders of IBS-D.

Rapid 3D radiofrequency field mapping using catalyzed double-angle method.

A new method is presented for rapid and accurate large volumetric radiofrequency (RF) field (B(1) (+)) mapping. This method is a modification of the double-angle method (DAM), which accelerates imaging speed and applies 3D acquisition to improve B(1) (+) measurement accuracy. It reduces repetition time and scan time by introducing a catalyzation RF pulse chain at the end of each DAM repetition cycle. The catalyzation pulse chain ensures that, after each TR period, the longitudinal magnetizations reach the same state for both measurements at two flip angles for the DAM so that the long TR requirement (TR >or= 5 T(1)) for complete relaxation of longitudinal magnetization of DAM becomes unnecessary. A multi-echo imaging sequence is additionally incorporated to further improve the efficiency of data acquisition. Simulations demonstrate an excellent flip angle measurement accuracy for catalyzed DAM even with TR << T(1). Phantom and in vivo volunteer studies are presented to demonstrate the catalyzation effect upon B(1)(+) mapping and the application of 3D catalyzed DAM for rapid and accurate large volume RF field mapping.

Development of a VX2 pancreatic cancer model in rabbits: a pilot study.

PURPOSE: An animal model of pancreatic cancer that is large enough to permit imaging and catheterization would be desirable for interventional radiologists to develop novel therapies for pancreatic cancer. The purpose of this study was to test the hypothesis that the VX2 rabbit model of pancreatic cancer could be developed as a suitable platform to test future interventional therapies. MATERIALS AND METHODS: The authors implanted and grew three pancreatic VX2 tumors per rabbit in six rabbits. Magnetic resonance (MR) imaging was performed at 2 weeks to confirm tumor growth. At 3 weeks, the authors selectively catheterized the gastroduodenal artery under guidance of x-ray digital subtraction angiography (DSA). T2-weighted anatomic imaging, diffusion-weighted MR imaging, and transcatheter intraarterial perfusion (TRIP) MR imaging were then performed. After imaging, tumors were confirmed at necropsy and histopathologically. Tumor sizes at 2 and 3 weeks were compared with a paired t test (P = .05). RESULTS: VX2 pancreatic tumors were grown in all six rabbits. The difference between tumor sizes at 2 and 3 weeks (1.29 cm +/- 0.39 vs 1.91 cm +/- 0.50, respectively) was significant (P < .001). All tumors were confirmed to be located within pancreatic tissue via histopathologic analysis. DSA and TRIP MR imaging were successful in five rabbits. Diffusion-weighted and anatomic MR imaging were successful in all six rabbits. CONCLUSIONS: The VX2 rabbit model of pancreatic cancer is feasible, as verified by imaging and pathologic correlation, and may be a suitable platform to test future interventional therapies.

Evaluation of Submillimeter Diffusion Imaging of the Macaque Brain Using Readout-Segmented EPI at 7 T.

OBJECTIVE: The purpose of the present study was to achieve submillimeter-level diffusion tensor imaging (DTI) of the macaque brain by using diffusion weighted (DW) readout-segmented echo planar imaging (rsEPI) with an optimized protocol at 7 T MRI. METHODS: Three anesthetized macaques were included in this study. Under different scan settings, we compared the signal-to-noise ratio (SNR) and geometric distortion of DW images, implemented an optimized protocol for submillimeter-level DTI acquisition, and evaluated its performance. RESULTS: The parallel-imaging-enabled (in GRAPPA mode) monopolar or monopolar+ diffusion scheme has higher SNR versus bipolar scheme, whereas trivial differences in SNR and image geometric distortion occurred when using increased readout segments with monopolar and monopolar+ that did not reach statistical significance. Submillimeter-level (0.8 mm isotropic) DTI data provide a sharper delineation of white matter contour than the 1 mm level. CONCLUSION: The rsEPI technique with parallel imaging enabled, and with the shortest readout segments in conjunction with monopolar/monopolar+ diffusion encoding scheme, may be optimal for submillimeter-level diffusion imaging over macaque brains in vivo. SIGNIFICANCE: rsEPI could effectively merit high-resolution DTI for in vivo macaque brain submillimeter structural architecture investigations at ultrahigh fields.