Washout Rate Research Articles

CARD21: The Effect of Drainage Cannula Design and Tip Position on Thrombosis Risk During Venoarterial Extracorporeal Membrane Oxygenation: A Computational Analysis

Background: Venoarterial extracorporeal membrane oxygenation (VA ECMO) supports critically ill patients with refractory cardiopulmonary failure. Drainage cannulae remove venous blood from the patient, but variability in cannula selection and tip position may impact flow dynamics and thrombosis risk. Therefore, this study investigated the effect of tip position of single-stage (SS) and multi-stage (MS) VA ECMO drainage cannulae on the risk of thrombosis. Methods: Computational fluid dynamics was used to model flow dynamics within a patient-specific geometry of the venae cavae. The tip of the SS and MS cannulae was modelled in the superior vena cava (SVC), SVC-Right atrium (RA) junction, mid-RA, inferior vena cava (IVC)-RA junction, and IVC. Constant mass flow rates were applied at all major vein inlets reflecting normal physiological flows. Drainage flow rates of the cannula were set at a constant 4 L/min throughout all simulations. The risk of thrombosis was assessed by measuring blood residence time, stagnant volume, rate of blood washout, and high wall shear stress. Results: Changes in the tip position of the SS cannula resulted in variability of thrombosis risk, whereas the MS cannula showed similar thrombosis risk during all simulations. The SS cannula showed reduced thrombosis risk arising from stagnant regions when placed in the SVC or SVC-RA junction, whereas an MS cannula was predicted to create stagnant regions during all tip positions (Figure 1). Conversely, the risk of thrombosis was increased in all positions with the SS cannula arising from higher maximum wall shear stresses (Table 1). When positioned in the IVC-RA junction and IVC, the SS cannula exhibited higher risk of thrombosis arising due to both high and low shear, compared to the MS cannula. Conclusion: Tip position of the drainage cannula impacts cannula flow dynamics and, subsequently, the risk of thrombosis. The use of MS cannulae can reduce high shear-related thrombosis, but SS cannulae can eliminate stagnant regions when advanced into the SVC. Therefore, the choice of cannula design and tip position should be carefully considered during cannulation.Figure 1. Comparison of stagnation regions between the single-stage (a) and multi-stage (b) cannulae at varying tip positions.

Thyroglobulin measurement in the needle washout for diagnosis of lymph node metastases of differentiated thyroid cancer

Introduction. Measurement of thyroglobulin (Tg) in a washout after fine-needle aspiration (FNA) is recommended for the diagnosis of metastases of differentiated thyroid cancer (DTC), but the method is not standardized and there is no recommended threshold value of Tg washout, which makes it difficult to interpret the results.Aim. To analyze Tg in the washout after FNA of lesions of different origin on the neck and to determine its optimal cutoff for the diagnosis of DTC metastases.Materials and methods. Ultrasound-guided FNA was performed in 1258 neck masses from 591 patients, 566 of them with confirmed DTC. In 1023 lesions, FNA was performed after thyroidectomy, 22 – after lobectomy, 213 – with preserved thyroid gland. The needle after FNA was washed in 1 ml of saline, in which the concentration of Tg was then examined. The level of Tg in the washout was compared with the histological (n = 522) or cytological diagnosis if no surgery was performed. The cut-off for Tg washout was determined by ROC analysis.Results. DTC lymph node metastases detected in 577 specimens. Nine specimens were obtained from metastases of thyroid cancer (TC) that does not express Tg (anaplastic TC, poorly differentiated TC, columnar-cell variant DTC), 22 – from neck metastases of other malignancy (lung cancer, mucinous soft tissues tumor, ovarian cancer, esophageal cancer, melanoma, neuroendocrine tumor), 6 – from other tumors of the neck (lymphoma, parathyroid adenoma, neurinoma). In 26 cases, the specimen was regarded as normal thyroid tissue left after thyroidectomy, 37 – postoperative seroma or granuloma, 1 – cyst of the neck, 578 – lymph node hyperplasia, 2 – sarcoidosis. The level of Tg washout from DTC metastasis and thyroid remnant significantly differed from that of non-thyroidal origin (p <0.0001). At the cut-off of 7.8 ng/ml, the sensitivity and specificity of Tg washout in the diagnosis of DTC metastases is 94 and 95 %, and at the cut-off of 20 ng/ml, 90 and 98 %, respectively. False-negative results were obtained from DTC with squamous metaplasia or sparse tumor cells in a specimen. False-positive results were obtained more often from lesions of level VI and IV compared with other localizations (8 % versus 4 %; p = 0.04). There were no differences in false positive rate in patients before and after thyroidectomy (p = 0.17), but in patients after thyroidectomy with a serum Tg >200 ng/ml, the false positive rate of Tg washout was significantly higher than that with a lower level of serum Tg (28 % versus 3 %; p = 0.0004). When comparing diagnostic performance of cytology and Tg washout, the advantage of the latter is in the diagnosis of cystic metastases, and the former is in the diagnosis of micrometastases and tumors that do not express Tg. Thyroglobulin in the washout increased the sensitivity of the cytology by 8 %. The combined use of these methods detected DTC metastases in 100 % of patients.Conclusion. Measurement of Tg in the washout is a useful addition to the cytology, increasing the diagnostic performance of the latter, mainly due to better detection of cystic metastases of DTC. The optimal suggested cut-off for Tg washout is 20 ng/mL, at which there are fewer false positives.

VueBox® perfusion analysis of dynamic contrast enhanced ultrasound provides added value in the diagnosis of small thyroid nodules.

To explore the potential added value of dynamic contrast enhanced ultrasound (DCE-US) using VueBox® software for the diagnosis of small solid thyroid nodules (≤1.0 cm). This prospective study was approved by the institutional review board and it was performed at two hospitals from January 2020 to October 2020. B mode ultrasound and contrast enhanced ultrasound (CEUS) images were obtained for 79 small solid thyroid nodules (≤1.0 cm) confirmed by ultrasound-guided fine needle aspiration cytology results in 79 consecutive patients (55 women and 24 men, median age: 41 years). The CEUS time-intensity curves (TICs) of thyroid nodules and surrounding parenchyma were created by VueBox® software (Bracco, Italy). The CEUS quantitative parameters were obtained after curve fitting. The diagnostic performance of CEUS and DCE-US was evaluated and compared. The weighted kappa statistic (κ) was performed to assess the interobserver agreement and consistency between the diagnosis of CEUS and DCE-US. Among the 79 thyroid nodules, 56 (70.9 %) were malignant and 23 (29.1 %) were benign lesions. Hypoenhancement during the arterial phase of CEUS was associated with malignancy (P < 0.001), with an AUC of 0.705 (sensitivity 71.4 %, specificity 69.6 %). Among all CEUS quantitative parameters, the peak enhancement (PE), wash-in rate (WiR), and wash-out rate (WoR) of DCE-US in malignancies were significantly lower than those in benign nodules (P = 0.049, P = 0.046, and P = 0.020, respectively). The area under the receiver operating characteristic curves (AUCs) of PE, WiR, and WoR were 0.642 (sensitivity 65.2 %, specificity 67.9 %), 0.643 (sensitivity 43.5 %, specificity 91.1 %), and 0.667 (sensitivity 69.6 %, specificity 69.6 %) in differentiation between benign and malignant small solid thyroid nodules (≤1.0 cm), respectively. Comparing the quantitative parameters of DCE-US between small solid thyroid nodules and surrounding normal thyroid parenchyma, the PE, WiAUC, WiR, wash-in perfusion index (WiPI), WoAUC, WiWoAUC, and WoR of the nodules were significantly lower than those of normal thyroid tissue (P = 0.008, P < 0.001, P = 0.037, P = 0.009, P = 0.003, P = 0.002, P = 0.049, respectively). A total of 16 (20.3 %) nodules showed isoenhancement during the arterial phase of CEUS, while the median PE ratio of surrounding tissue and thyroid nodules was 1.70 (IQR: 1.33-1.89). VueBox® is a helpful tool for the evaluation of dynamic microvascularization of thyroid nodules, and DCE-US using VueBox® perfusion analysis could provide added values for differential diagnosis of small solid thyroid nodules (≤1.0 cm).

Preoperative prediction of Ki-67 status in invasive breast carcinoma using dynamic contrast-enhanced MRI, diffusion-weighted imaging and diffusion tensor imaging

BackgroundThe Ki-67 is a beneficial marker of tumor aggressiveness. It is proliferation index that has been used to distinguish luminal B from luminal A breast cancers. By fast progress in quantitative radiology modalities, tumor biology and genetics can be assessed in a more accurate, predictive, and cost-effective method. The aim of this study was to assess the role of dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging and diffusion tensor imaging in prediction of Ki-67 status in patients with invasive breast carcinoma estimate cut off values between breast cancer with high Ki-67 status and those with low Ki-67 status.ResultsCut off ADC (apparent diffusion co-efficient) value of 0.657 mm2/s had 96.4% sensitivity, 75% specificity and 93.8% accuracy in differentiating cases with high Ki67 from those with low Ki67. Cut off maximum enhancement value of 1715 had 96.4% sensitivity, 75% specificity and 93.8% accuracy in differentiating cases with high Ki67 from those with low Ki67. Cut off washout rate of 0.73 I/S had 60.7% sensitivity, 75% specificity and 62.5% accuracy in differentiating cases with high Ki67 from those with low Ki67. Cut off time to peak value of 304 had 71.4% sensitivity, 75% specificity and 71.9% accuracy in differentiating cases with high Ki67 from those with low Ki67.ConclusionsADC, time to peak and maximum enhancement values had high sensitivity, specificity and accuracy in differentiating breast cancer with high Ki-67 status from those with low Ki-67 status.

1H-MRS to evaluate improved triglyceride accumulation in idiopathic triglyceride deposit cardiomyovasculopathy after CNT-01 (tricaprin/trisdecanion) administration.

Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride (TG) accumulation in the myocardium and coronary arteries caused by genetic or acquired dysfunction of adipose TG lipase (ATGL). A phase IIa trial has been conducted involving patients with idiopathic TGCV using CNT-01 (tricaprin/trisdecanion) by the Japan TGCV study group, which showed that CNT-01 improved myocardial lipolysis as demonstrated by iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) scintigraphy. We evaluated changes in myocardial TG content using proton magnetic resonance spectroscopy (1H-MRS) before/after CNT-01. This report describes a male patient with hypertension, diabetes, angina pectoris, repeated percutaneous coronary intervention, chest pain, and exertional dyspnea that persisted despite standard medications and nitroglycerin. Idiopathic TGCV was diagnosed based on a remarkably reduced washout rate (WR) for BMIPP scintigraphy, high myocardial TG content on 1H-MRS, and no ATGL mutation. After an 8-week, 1.5 g/day CNT-01 administration, the WR of BMIPP increased from 5.1 to 13.3% and the myocardial TG content decreased from 8.4 to 5.9%, with no adverse effects. CNT-01 corrected myocardial lipolysis and subsequently reduced TG content in idiopathic TGCV as evaluated using 1H-MRS, which may be a useful, noninvasive evaluation of therapeutic efficacy. Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride accumulation in the myocardium and coronary arteries, caused by genetic or acquired dysfunction of adipose triglyceride lipase. Japan TGCV Study Group developed a specific treatment for idiopathic TGCV using CNT-01 (tricaprin/trisdecanion), a type of medium-chain fatty acid. CNT-01 corrected myocardial lipolysis and reduced TG content in idiopathic TGCV using proton magnetic resonance spectroscopy, which may be a useful noninvasive evaluation of therapeutic efficacy.

Left-atrial volume reduction reflects improvement of cardiac sympathetic nervous function in patients with severe aortic stenosis after transcatheter aortic valve replacement.

Trans-catheter aortic valve replacement (TAVR) is an excellent alternative intervention for surgical aortic valve replacement. Cardiac sympathetic nervous (CSN) function and left atrial (LA) volume are both important prognostic factors in patients with aortic stenosis (AS) after TAVR. The relationship between the two clinical factors is unknown, however. This retrospective observational study aimed to assess the correlation between CSN function and LA volume in 48 symptomatic patients with severe AS (median age: 85years, IQR 82-88years; 81% female) before and after TAVR. CSN function was assessed by performing 123I-metaiodobenzylguanidine (MIBG) scintigraphy before and 6months after TAVR, and the delayed heart-to-mediastinum ratio (dHMR) and washout rate (WR) were calculated. We also performed transthoracic echocardiography near the same time. TAVR improved the dHMR, WR, and LA volume index (LAVI) (dHMR: median 2.89 [IQR 2.62-3.23] vs. 2.98 [2.49-3.25], p = 0.0182; WR: 28% [24-38] vs. 23% [16-32], p < 0.0001; LAVI: 47.7mL/m2 [37.8-56.3] vs. 41.2mL/m2 [33.7-56.1], p = 0.0024). In multiple linear regression analysis, the percentage change in LAVI from baseline to post-TAVR (∆LAVI%) was an independent predictor of change in dHMR from baseline to post-TAVR (β = - 0.35, p = 0.0110). In conclusion, LA volume reduction reflected CSN functional improvement after TAVR. In patients with TAVR, ∆LAVI% might be a valuable parameter for evaluating CSN functional recovery.

4D digital anthropomorphic breast phantom for iodinated contrast-enhanced imaging.

Differentiating between benign and malignant masses is one of the biggest challenges in breast imaging. The challenge is ingrained in the similarity of the attenuation coefficients between different types of lesion tissues and fibroglandular tissues. Contrast-enhanced imaging techniques can take advantage of the differing metabolism in different tissues, therefore, potentially allowing better differentiation of malignant and benign lesions. To facilitate the development and optimization of such technologies, we propose a fully digital 4D phantom that features time-varying enhancement patterns for different tissue types. The 4D model is based on a static, anthropomorphic 3D digital breast phantom. Masses inserted into the 3D phantom are based on a previously published model. Physiological parameters that capture the key characteristics of masses, e.g., wash-in and wash-out rates indicating metabolic level, are employed in the model to simulate fundamental features for categorizing mass types. The two-compartmental model, a well-known model in the field of pharmacokinetics, is used to depict the diffusion process of the contrast agent. Two methods are proposed to allow for the simulations of lesions with necrotic cores of varying shapes and sizes. The fourth dimension of the phantom models different time-varying enhancement patterns for different materials including fibroglandular tissue and lesion tissue. Metabolic characteristics of mass models can be adjusted to provide different enhancement patterns. The parameters of the 4D phantom can also be adjusted to fit different scenarios. The usage of the phantom is demonstrated by simulating mammograms at different time frames. A 4D digital anthropomorphic breast phantom that models different time-varying contrast enhancement patterns is presented. This phantom could be an integral tool for use in in silico trials to assess image quality of iodinated contrast-enhanced mammography, digital breast tomosynthesis, and breast computed tomography systems.

The effect of drainage cannula tip position on risk of thrombosis during venoarterial extracorporeal membrane oxygenation

Background and objectivesVenoarterial extracorporeal membrane oxygenation (VA ECMO) is able to support critically ill patients undergoing refractory cardiopulmonary failure. It relies on drainage cannulae to extract venous blood from the patient, but cannula features and tip position may impact flow dynamics and thrombosis risk. Therefore, this study aimed to investigate the effect of tip position of single-stage (SS) and multi-stage (MS) VA ECMO drainage cannulae on the risk of thrombosis. MethodsComputational fluid dynamics was used to model flow dynamics within patient-specific geometry of the venous vasculature. The tip of the SS and MS cannula was placed in the superior vena cava (SVC), SVC-Right atrium (RA) junction, mid-RA, inferior vena cava (IVC)-RA junction, and IVC. The risk of thrombosis was assessed by measuring several factors. Blood residence time was measured via an Eulerian approach through the use of a scalar source term. Regions of stagnant volume were recognised by identifying regions of low fluid velocity and shear rate. Rate of blood washout was calculated by patching the domain with a scalar value and measuring the rate of fluid displacement. Lastly, wall shear stress values were determined to provide a qualitative understanding of potential blood trauma. ResultsThrombosis risk varied substantially with position changes of the SS cannula, which was less evident with the MS cannula. The SS cannula showed reduced thrombosis risk arising from stagnant regions when placed in the SVC or SVC-RA junction, whereas an MS cannula was predicted to create stagnant regions during all tip positions. When positioned in the IVC-RA junction or IVC, the risk of thrombosis was higher in the SS cannula than in the MS cannula due to both high and low shear flow. ConclusionTip position of the drainage cannula impacts cannula flow dynamics and, subsequently, the risk of thrombosis. The use of MS cannulae can reduce high shear-related thrombosis, but SS cannulae can eliminate stagnant regions when advanced into the SVC. Therefore, the choice of cannula design and tip position should be carefully considered during cannulation.

Early Effect of Transcatheter Mitral Valve Repair on Cardiac Sympathetic Nerve Activity

BackgroundCardiac sympathetic nerve activity (SNA) is overactivated in heart failure patients and associated with clinical outcomes. The aim of this study is to investigate the early effect of MitraClip repair on cardiac SNA. MethodsWe evaluated the change of cardiac SNA by 123I- meta-iodobenzylguanidine (MIBG) scintigraphy in patients who underwent MitraClip repair from March 2019 to June 2020 in our hospital. Patients without acute procedural success were excluded, including patients who died or underwent mitral valve surgery before discharge. MIBG scintigraphy was performed at baseline and 1 ​month after MitraClip repair. ResultsWe analyzed 48 patients (mean age 78.6 ± 10 years; 52.1% male; 37 secondary mitral regurgitation [SMR]/11 primary mitral regurgitation [PMR]). MR severity and New York Heart Association functional class significantly improved from baseline to 1 ​month after MitraClip repair (both p < 0.001). Overall, delay heart-mediastinum ratio (H/M) had no significant change, and washout rate (WR) showed a decreasing trend (delay H/M; pre 2.07 ± 0.46, post 2.05 ± 0.49, paired p = 0.348, WR; pre 36.1 ± 11.6%, post 33.6 ± 11.7%, paired p = 0.061). In PMR patients, WR was significantly decreased, however, delay H/M was not (delay H/M; pre 2.15 ± 0.50, post 2.10 ± 0.57, paired p = 0.019, WR; pre 34.6 ± 10.5%, post 26.7 ± 13.8%, paired p = 0.568). In contrast, in SMR patients, neither delay H/M nor WR were significantly changed (delay H/M; pre 2.05 ± 0.45, post 2.03 ± 0.47, paired p = 0.474, WR; pre 36.6 ± 11.9%, post 35.7 ± 10.4%, paired p = 0.523). ConclusionsOur study demonstrates that MitraClip repair could significantly decrease cardiac SNA of WR in PMR patients during 1-month follow-up, however, in SMR patients, the significant change of MIBG parameters was not observed.

Three-Dimensional Heart Segmentation and Absolute Quantitation of Cardiac 123I-metaiodobenzylguanidine Sympathetic Imaging Using SPECT/CT.

Background: A three-dimensional (3D) approach to absolute quantitation of 123I-metaiodobenzylguanidine (MIBG) sympathetic nerve imaging using single-photon emission tomography (SPECT) / computed tomography (CT) is not available. Therefore, we calculated absolute cardiac counts and standardized uptake values (SUVs) from images of 72 consecutive patients with cardiac and neurological diseases using 123I-MIBG SPECT/CT and compared them with conventional planar quantitation. We aimed to develop new methods for 3D heart segmentation and the quantitation of these diseases. Methods: We manually segmented early and late SPECT/CT images of the heart in 3D, then calculated mean (SUVmean) and maximum (SUVmax) SUVs. We analyzed correlations between SUVs and planar heart-to-mediastinum ratios (HMRs), and between washout rates (WRs) derived from the SUVs and planar data. We also categorized WRs as normal or abnormal using linear regression lines determined by the relationship between SPECT/CT and planar WRs, and assessed agreement between them. Results: We calculated SUVmean and SUVmax from all early and late 123I-MIBG SPECT/CT images. Planar HMRs correlated with early and late SUVmean (R2=0.59 and 0.73, respectively) and SUVmax (R2=0.46 and 0.60, respectively; both p<0.0001). The SPECT/CT WRs determined based on SUVmean and SUVmax (R2=0.79 and 0.45, p<0.0001) closely correlated with planar WRs. Agreement of high and low WRs between planar WRs and SPECT/CT WRs calculated using SUVmax and SUVmean reached 88.1% and 94.4% respectively. Conclusions: We found that sympathetic nervous activity could be absolutely quantified in 3D from 123I-MIBG SPECT/CT images. Therefore, we propose a new method for quantifying sympathetic innervation on SPECT/CT images.

Practice Recommendation for Measuring Washout Rates in 123I-BMIPP Fatty Acid Images.

The purpose of this practice recommendation is to specifically identify the critical steps involved in performing and interpreting 123I-β-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and measurement of washout rate (WR) from the heart. This document will cover backgrounds, patient preparation, testing procedure, visual image interpretation, quantitation methods using planar and SPECT studies, and reporting of WR. The pitfall and some tips for the calculation of 123I-BMIPP WR are also included. The targets of global and regional WR calculation include ischemic heart disease, cardiomyopathy, heart failure, and triglyceride deposit cardiomyovasculopathy, an emerging rare heart disease.

Simulating Dynamic of Suspended Sediment Flow Based on Data of Primorskaya Water Balance Station

Soil loss rate, suspended load, and suspended sediment discharge were simulated for the drainage basin of the Komarovka R., located at the territory of the former Primorskaya Water Balance, Russian Far East. The study was based on an open-code SWAT model. The model was calibrated and verified using archive measurement data on sediment load and suspended sediment discharge at PWBS by data of Tsentral’nyi hydrological gage (157 km2). The simulation efficiency of the suspended load and suspended sediment discharge corresponds to categories satisfactory and higher. On the average for the drainage basin, the rate of soil washout is 11–12 t/ha per year. The washout rate is maximal in the period of active snow melting. The mean monthly value for April–May is 75 thous. t. The mean annual washout is 171 thous. t, and the maximal is 800 thous. t/year. The mean annual runoff of suspended sediments in the outlet section of the drainage basin is 2.6 thous. t. The highest monthly values of sediment runoff correspond to the period of summer floods in August, when with average of 1 thous. and maximum of 7.7 thous. t. The obtained data on the heterogeneity of the spatial distribution of the simulated values of washout rate are in good agreement with the landscape and climatic features of runoff formation in the drainage river basin. The major errors in the estimation of sediment load are due to the simulation quality of the hydrological regime and dynamics of runoff components that form flood hydrographs.

Carnitine Administration and 123I-BMIPP Washout Rate in Hemodialysis Patients with Triglyceride Deposit Cardiomyovasculopathy.

Triglyceride deposit cardiomyovasculopathy (TGCV) is an emerging rare heart disease with high mortality, characterized by defective intracellular lipolysis of triglycerides (TG). We developed diagnostic criteria for TGCV, in which low washout rate of BMIPP (BMIPP-WR) is a key factor. The working group of the Japan Society of Nuclear Cardiology recently published practice recommendations for measuring BMIPP-WR. We reported that hemodialysis (HD) patients with TGCV exhibited a markedly higher cardiovascular risk than those without TGCV. Secondary carnitine deficiency is common in patients undergoing HD, as carnitine is removed from the circulation. However, clinical evidence linking carnitine levels to BMIPP-WR is limited. Here we report the effect of L-carnitine administration on the BMIPP-WR in 9 chronic HD patients with TGCV in a retrospective cohort. The mean age at TGCV diagnosis was 59 years. Following standard doses of oral L-carnitine administration, plasma free carnitine levels significantly increased. However, BMIPP-WR was not changed. In normal condition, most BMIPP taken up were esterified/incorporated into TG pool, hydrolyzed by intracellular lipases, and then transported by carnitine shuttle to mitochondria. In TGCV, intracellular TG lipolysis is defective. During the intracellular metabolism of BMIPP, carnitine shuttling occurs downstream of TG lipolysis. Therefore, even when carnitine levels were increased, BMIPP-WR did not change in patients with TGCV who underwent chronic HD. A phase IIb/III clinical trial for TGCV, is underway (jRCT2051210177). Increased awareness of the disease concept of TGCV, along with its diagnostic principles and procedures using BMIPP scintigraphy, is warranted.

Assessment of Meningeal Lymphatics in the Parasagittal Dural Space: A Prospective Feasibility Study Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

Meningeal lymphatic vessels are predominantly located in the parasagittal dural space (PSD); these vessels drain interstitial fluids out of the brain and contribute to the glymphatic system. We aimed to investigate the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the dynamic changes in the meningeal lymphatic vessels in PSD. Eighteen participants (26-71 years; male:female, 10:8), without neurological or psychiatric diseases, were prospectively enrolled and underwent DCE-MRI. Three regions of interests (ROIs) were placed on the PSD, superior sagittal sinus (SSS), and cortical vein. Early and delayed enhancement patterns and six kinetic curve-derived parameters were obtained and compared between the three ROIs. Moreover, the participants were grouped into the young (< 65 years; n = 9) or older (≥ 65 years; n = 9) groups. Enhancement patterns and kinetic curve-derived parameters in the PSD were compared between the two groups. The PSD showed different enhancement patterns than the SSS and cortical veins (P < 0.001 and P < 0.001, respectively) in the early and delayed phases. The PSD showed slow early enhancement and a delayed wash-out pattern. The six kinetic curve-derived parameters of PSD was significantly different than that of the SSS and cortical vein. The PSD wash-out rate of older participants was significantly lower (median, 0.09; interquartile range [IQR], 0.01-0.15) than that of younger participants (median, 0.32; IQR, 0.07-0.45) (P = 0.040). This study shows that the dynamic changes of meningeal lymphatic vessels in PSD can be assessed with DCE-MRI, and the results are different from those of the venous structures. Our finding that delayed wash-out was more pronounced in the PSD of older participants suggests that aging may disturb the meningeal lymphatic drainage.

Distinguishing mesorectal tumor deposits from metastatic lymph nodes by using diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in rectal cancer.

This study aimed to identify whether apparent diffusion coefficient (ADC) values and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters are helpful in distinguishing mesorectal tumor deposits (TD) from metastatic lymph nodes (MLN) in rectal cancer (RC). Thirty patients (59 lesions, including 30 TD and 29 MLN) with RC who underwent pretreatment-MRI between February 2016 and August 2018 were enrolled. The morphological features, ADC values, and semi-quantitative parameters of DCE-MRI, including relative enhancement (RE), maximum enhancement (ME), maximum relative enhancement (MRE), time to peak (TTP), wash-in rates (WIR), wash-out rates (WOR), brevity of enhancement (BRE), and area under the curve (AUC) were measured on lesions (TD or MLN) and RC. The parameters were compared between TD and MLN, tumor with and without TD group by using Fisher's exact test, independent-samples t-test, and Mann-Whitney U test. The ratio (lesion-to-tumor) of the parameters was compared between TD and MLN. Receiver operating characteristic curve analysis and binary logistic regression analysis were used to assess the diagnostic ability of single and combined metrics for distinguishing TD from MLN. The morphological features, including size, shape, and border, were significantly different between TD and MLN. TD exhibited significantly lower RE, MRE, RE-ratio, MRE-ratio, ADCmin-ratio, and ADCmean-ratio than MLN. RE-ratio showed the highest AUC (0.749) and accuracy (77.97%) among single parameters. The combination of DCE-MRI and DWI parameters together showed higher diagnostic efficiency (AUC = 0.825). Morphological features, ADC values, and DCE-MRI parameters can preoperatively help distinguish TD from MLN in RC. • DWI and DCE-MRI can facilitate early detection and distinguishing mesorectal TD (tumor deposits) from MLN (metastatic lymph nodes) in rectal cancer preoperatively. • TD has some specific morphological features, including relatively larger size, lower short- to long-axis ratio, irregular shape, and ill-defined border on T2-weighted MR images in rectal cancer. • The combination of ADC values and semi-quantitative parameters of DCE-MRI (RE, MRE) can help to improve the diagnostic efficiency of TD in rectal cancer.

Regenerative Efficacy of Supercritical Carbon Dioxide-Derived Bone Graft Putty in Rabbit Bone Defect Model.

Bone defects can arise from numerous reasons, such as aging, tumor, trauma, infection, surgery, and congenital diseases. Bone grafts are commonly used as a substitute to fill the void and regenerate the defect. Due to its clean and green technology, the supercritical carbon dioxide (SCCO2) extraction aided the production of bone grafts is a recent trend. The SCCO2-derived bone graft has osteoconductive and osteoinductive properties along with excellent biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical properties; however, clinical usage during surgery is time-consuming. Therefore, we produced a putty material combining bone graft powder and acellular dermal matrix (ADM) powder and tested its regenerative efficacy in the critical defect in the rabbit model. The putty was found to retain the tubular structure. In addition, the putty depicted excellent stickiness and cohesiveness in both saline and blood medium. The bone regeneration of bone graft and putty was similar; both had excellent bone healing and regeneration of critical defects as evaluated by the X-ray, microtomography, hematoxylin-eosin, Masson trichrome, and alizarin red staining. Putty contains a less washout rate, good mechanical strength, and biocompatibility. In conclusion, the SCCO2-derived moldable putty could be a promising easy-to-use alternative for bone grafts at present which might have real-world usage in orthopedics as a potential bone void filler and dental socket preservation.

Clinical findings of triglyceride deposit cardiomyovasculopathy

Abstract Background Triglyceride (TG) deposit cardiomyovasculopathy (TGCV) is a novel cardiovascular disorder and was recently encoded as an orphan disease in Europe (ORPHA code: 565612). Defective intracellular lipolysis results in TG accumulation in the myocardium and coronary arteries in TGCV. The myocardial washout rate (WR) of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is an essential indicator to evaluate myocardial lipolysis in vivo, and decreased WR (&amp;lt;10%) of BMIPP is one of the essential items of diagnostic criteria for TGCV. Purpose To clarify clinical findings of TGCV including comorbid conditions and laboratory findings. Methods We enrolled 234 patients who underwent BMIPP scintigraphy between September 2015 and July 2019. The distributions of TGCV in each comorbidity, cardiac functions and laboratory findings were investigated. Results In total, 104 patients were diagnosed with definitive TGCV. The BMIPP WR of TGCV patients was −1.37±10.6%. TGCV patients had various comorbid conditions, including coronary artery disease (75%), diabetes mellitus (56%), and heart failure (21%). Left ventricular ejection fraction (LVEF) of TGCV patients was significantly lower than that of non-TGCV patients (38.1±18.0% vs. 43.6±18.9%, p-value=0.026). Moreover, among those who did not take lipid-lowering drugs, there was no difference in the serum TG level between TGCV and non-TGCV patients (TGCV: n=44, 127±84.6 mg/dL, non-TGCV: n=66, 133±70.7 mg/dL, p-value=0.73). Conclusions TGCV patients showed multiple coexistence of coronary artery disease, diabetes mellitus, or heart failure with lower LVEF. Serum TG level was not significantly different between TGCV and non-TGCV patients. Serum TG did not affect the intracellular TG accumulation in TGCV patients directly, and this result was consistent with the pathophysiological hypothesis that the TG accumulation in the myocardial cytoplasm is due to intracellular lipase dysfunction. Funding Acknowledgement Type of funding sources: None.

Impaired cardiac sympathetic innervation activity is associated with myocardial extracellular remodeling, functional capacity and biomarkers

Abstract Background Despite recent advances in treatment, heart failure (HF) continues to be associated with high mortality rates. In this setting, 123iodine-meta-iodobenzylguanidine (123I-MIBG) scintigraphy emerges as a promising tool for the prediction of clinical outcomes in HF due to its ability to assess cardiac sympathetic innervation. However, 123I-MIBG scintigraphy's correlation with myocardial remodeling and cardiopulmonary exercise capacity has not yet been fully elucidated. Objectives To evaluate cardiac sympathetic activity through 123I-MIBG scintigraphy, and to analyze its correlation with myocardial remodeling and exercise capacity in HF patients. Methods Symptomatic HF patients (NYHA class II–III) stratified by LVEF as HFpEF (LVEF 45%) and HFrE'F (LVEF &amp;lt;45%) and healthy controls were enrolled. HF patients were euvolemic under optimized treatment at the time of enrollment. All individuals underwent CMR with morphology/function and extracellular volume fraction (ECV) assessment, global longitudinal strain (GLS) by echocardiogram, cardiopulmonary exercise testing (CPET), cardiac sympathetic imaging 123I-MIBG scintigraphy (mIBG), and NT-proBNP. Results Eighty individuals were recruited allocated into the following groups: HFpEF (n=33, 59.42±12.63 years, LVEF: 59.82±9.87, NT-proBNP: 409.40±693.37, H2FPEF-score: 5±2), HFrEF (n=28, 53.93±11.40 years; LVEF: 29.81±8.67, NT-proBNP: 1662,34±2016,73) and healthy controls (42.65±13.96 years, LVEF: 65.27±4.73, NT-proBNP: 44,43±33,28) were enrolled. While ECV was elevated in HF groups (HFpEF: 0.32±0.05%, HFrEF: 0.31±0.41% and controls: 0.26±0.03, p&amp;lt;0.05), adjusted maximum oxygen consumption (VO2max) was markedly reduced vs. controls (HFpEF: 18.58±6.29mL/kg/min, HFrEF: 17.60±3.89mL/kg/min, controls: 29.73±9.98mL/kg/min, p&amp;lt;0.001). The MIBG heart-to-mediastinum ratio at 4 hours (H/M) was significantly lower in HF compared with controls (HFpEF: 1.59±0.25, HFrEF: 1.45±0.15 and controls: 1.92±0.25, p&amp;lt;0.001). Interestingly, the H/M ratio was more impaired with HFrEF compared to HFpEF (Fig. 1A). As a result, the mean myocardial washout rate was increased in HF patients (HFrEF 36.38±14.35, HFpEF 29.92±18.33 vs. controls 8.0±27.01, p&amp;lt;0.001). In addition, considering all HF patients, H/M was inversely associated with ECV (R: −0.45, p&amp;lt;0.001, Fig. 1B), NT-proBNP (R: −0.55, p&amp;lt;0.001) and VO2max (R: −0.27, p: &amp;lt;0.024, Fig. 1C). GLS was inversely associated with H/M in HFrEF but not HFpEF (HFrEF: R: −0.535, p&amp;lt;0.001 and HFpEF: R: −0.036, p=NS, Fig. 1D). Conclusion Cardiac sympathetic activity assessed by 123I-MIBG was abnormal in patients with HF with reduced and preserved EF as compared to controls. H/M, a validated marker for cardiac sympathetic activity, showed a strong correlation with markers of functional capacity and myocardial remodeling. Sympathetic innervation appears to be a limiting factor for global longitudinal strain in HFrEF, while in HFpEF longitudinal strain is independent of sympathetic activity Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The São Paulo Research Foundation

Effects of mineralocorticoid receptor antagonist eplerenone on cardiac sympathetic nerve activity and left ventricular remodeling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction

PurposeThe activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine and promotes structural remodeling of the heart. The mineralocorticoid receptor antagonist (MRA) eplerenone prevents left ventricular (LV) remodeling in patients with acute myocardial infarction, but its influence on cardiac sympathetic nerve activity (CSNA) has not been determined. MethodsWe retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Eighty-four STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients who treated with MRA (N = 42), and those who did not (N = 42). The LV end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography, and plasma procollagen type III amino terminal peptide (PIIINP) was measured before and 3 weeks after treatment. The delayed total defect score (TDS), delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined using 123I-MIBG scintigraphy after 3 weeks. ResultsFollowing primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the MRA group showed significantly lower TDS and WR values (TDS: 22.8 ± 8.1 vs 32.2 ± 11.5, P < 0.005; WR: 31.1 ± 9.0% vs 42.7 ± 9.9%, P < 0.001) and a significantly higher H/M ratio (2.23 ± 0.41 vs 2.03 ± 0.36, P < 0.05) than the non-MRA group. The degree of change in LV parameters, and PIIINP were more favorable in the MRA group than in the non-MRA group. Moreover, multiple linear regression analyses revealed that both WR and not MRA treatment were significant predictor for LV remodeling, along with PIIINP concentrations. ConclusionAdministration of eplerenone improves CSNA and prevents LV remodeling in patients with a first STEMI.

Cardiac 123I-mIBG scintigraphy for prediction of catheter ablation outcome in patients with atrial fibrillation

BackgroundPrevious studies show inconsistent results on the role of innervation imaging (with 123I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post-CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF. Methods123I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patient was followed for 12 months. ResultsMultivariable analysis demonstrated that late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/Mlate <1.6 (sensitivity 73.53%, specificity 81.3%, AUC 0.792, P < .001) and WR > 25.11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0.712, P < .001) indicate high probability of AF relapses during 12 months after CA. ConclusionPre-CA parameters of global cardiac sympathetic activity estimated by 123I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients with normal LVEF and absence of significant CAD.