Washout Rate Research Articles

Absolute and Relative Washout Rates Associated With Parathyroid Adenoma.

Background Parathyroid adenoma is a benign parathyroid gland tumor that causes excessive parathyroid hormone production, leading to primary hyperparathyroidism. High serum calcium levels characterize it. Accurate diagnosis and localization of adenomas are crucial for effective surgical management. Computed tomography is a fundamental imaging technique used to identify and characterize parathyroid adenomas. This study aimed to provide a comprehensive overview of the absolute and relative contrast washout rates of parathyroid adenoma and the thyroid gland, and compare enhancement patterns to establish the absolute and relative washout rates of parathyroid adenoma. Materials & methods This retrospective study analyzes the CT findings of 33 patients with histopathologically proven parathyroid adenomas. All patients with 4D CT scans have been included with no exclusion criteria. The mean attenuation was measured in Hounsfield units for the parathyroid adenoma and thyroid gland in the non-enhancing, arterial, venous, and delayed phases, depending on the region of interest. All statistical analyses were performed using SPSS (IBM Corp., Armonk, NY, USA). Student's t-test was used to evaluate the differences in measurements between the parathyroid adenoma and thyroid tissue. One-way ANOVA was used to evaluate the difference in calculations between the parathyroid adenoma and thyroid tissue. P-values <0.001 were considered statistically significant. Results The most common location of parathyroid adenomas is inferior to the thyroid gland. The average pre-contrast attenuation of the parathyroid adenoma is 61.8 ± 15.5 HU compared to 105.5 ± 15.2 HU of the thyroid gland. The arterial attenuation of the parathyroid adenoma is 170.3 ± 40.7 HU, relatively comparable to the thyroid gland arterial attenuation, which is 188.0 ± 9.6 HU. The venous and delayed-phase attenuation of the parathyroid adenoma were 146.8 ± 37.5 and 96.8 ± 26.7 HU, respectively,and 178.8 ± 20.2 HU and 149.3 ± 15.2 HU for the thyroid gland, respectively. The calculated absolute and relative arterial washout rates for the parathyroid adenoma were 69.4 ± 13.4% and 43.2 ± 8.0%, respectively, as compared to 46.4 ± 9.9% and 20.6 ± 6.7% for the thyroid gland. The calculated absolute and relative venous washout rates for the parathyroid adenoma were 58.0 ± 21.4% and 33.0 ± 13.7%, respectively, as compared to 37.2 ± 17.2% and 15.9 ± 9.6% for the thyroid gland. Conclusions Parathyroid adenoma demonstrated a significantly higher washout rate than the thyroid gland tissue. Absolute arterial washout ≥69% and relative arterial washout ≥43% indicate parathyroid adenoma. Moreover, absolute venous washout ≥58% and relative venous washout ≥33% can be considered diagnostic factors for parathyroid adenoma. Further, pre-contrast attenuation of <60 Hounsfield units has a substantial predictive value for parathyroid adenoma in addition to the described washout rate. Increased awareness of the washout rate can increase the success rate of four-dimensional computed tomography interpretation.

Comparison of calculation algorithms between arithmetic mean of washout rate and total-count-based washout rate in single-photon emission computed tomography

Abstract Background Myocardial washout rate (WR) analysis of radiopharmaceuticals is utilized in nuclear cardiology to evaluate the clinical pathophysiology of the heart. WR is defined as the ratio of the difference between the count in the early image and the time-decay-corrected delayed image divided by the former. The arithmetic mean of washout rate (AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computed tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. Therefore, we newly formulated a modified algorithm for calculating WR based on the total count (TCWR). Purpose To clarify the usefulness of TCWR by comparing the calculation algorithms between TCWR and AMWR. Methods The WR of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. We focused on the patients with specific conditions that decreased BMIPP uptake in the early image — CD36 deficiency is a human loss-of-function genetic mutation model for BMIPP uptake, and old myocardial infarction (OMI) may present such a clinical phenotype. Also, patients with triglyceride deposit cardiomyovasculopathy (TGCV) were enrolled since a markedly decreased BMIPP WR (&amp;lt;10%) is one of the essential criteria for its diagnosis. Consecutive patients who underwent BMIPP scintigraphy were reviewed, and the analysis included patients without detectable cardiovascular diseases (normal) (n = 11), those with CD36 deficiency (n = 6), TGCV (n = 14), TGCV with OMI (n = 17), and non-TGCV with OMI (n = 10). Results WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4 ± 8.5 and 27.3 ± 8.5% (p = 0.97); CD36 deficiency, -3.2 ± 6.5 and -4.1 ± 7.4% (p = 0.81); TGCV, 2.4 ± 6.3 and 2.2 ± 6.3% (p = 0.93); and TGCV with OMI, -0.9 ± 7.6 and -3.7 ± 8.4% (p = 0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8 ± 8.7 and 18.9 ± 6.7%, p = 0.0008). Conclusions TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.Definition of calculation algorithms.Comparison of TCWR and AMWR.

Remote ischemic peri-conditioning suppressed the activation of cardiac sympathetic nervous system in patients with acute myocardial infarction: a randomized controlled trial

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). Remote ischemic peri-conditioning (RIPC) is reported to improve clinical outcome in patients with AMI. However, there is not fully clarified whether RIPC could have an effect on cardiac sympathetic activity. Purpose The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic activity in patients with AMI. Methods We randomly assigned 157 patients with suspected AMI undergoing emergent percutaneous coronary intervention to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80) upon arrival to the cardiac catheterization laboratory. After excluding inappropriate patients such as those who were diagnosed with other than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). The primary endpoint was cardiac sympathetic activity assessed by the cardiac MIBG imaging washout rate (WR) at discharge and 1 year after discharge. WR and late heart-to-mediastinum ratio (HMR) in cardiac MIBG was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Results Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. There was no significant difference in WR between two groups at discharge. Although WR was significantly decreased 1 year after the discharge in both groups, patients in RIPC group showed significantly lower WR than those in control group (22.0 [15.1-30.6]% and 26.5 [18.4-34.4]%, p=0.0269) 1 year after the discharge. Late HMR significantly decreased during 1-year follow-up in patients only in RIPC group (p=0.0133) and patients in RIPC group tended to show higher late HMR compared to those in control group (2.01 [1.79-2.25] and 1.92 [1.72-2.11], p=0.0581) 1 year after the discharge. Conclusion(s) Remote ischemic peri-conditioning could suppress the augmented cardiac sympathetic activity in patients with acute myocardial infarction during 1-year follow-up.

Abstract 15399: Cardiac Sympathetic Nerve Activity in Women With a History of Takotsubo Syndrome: A Novel Stress Myocardial Radionuclide Imaging Strategy

Introduction: Takotsubo syndrome (TTS) is characterized by transient left ventricular (LV) systolic dysfunction, triggered by physical or emotional stress, and associated with increased long-term cardiovascular morbidity. Cardiac iodine-123-meta-iodobenzylguanidine (mIBG) imaging has previously demonstrated sympathetic hyperactivity in the TTS subacute state which improves at follow-up during rest imaging. Cardiac neuronal dysfunction in response to stress has not been evaluated in recovered TTS. Hypothesis: Sympathetic hyperactivity, as measured by stress mIBG, is abnormal in TTS after recovery of LV ejection fraction (LVEF). Methods: To elicit a sympathetic challenge, women with history of TTS with recovered LVEF (n=19) and asymptomatic age- and sex-matched reference controls (n=10) underwent treadmill (6 minutes) with simultaneous mental-stress testing (public speaking with anger recall). mIBG (10 mCi) was injected during exercise, and planar and SPECT imaging were performed at 15 min (early) and 240 min (late), followed by Tc-99m tetrofosmin myocardial perfusion imaging. Early and late heart-to-mediastinal ratio (HMR) and washout rate (WR) corrected for background were calculated. Results: Median time from last TTS event was 23 months (range 4-56). Overall mean age was 60± 12 years, body mass index 25 ± 4kg/m 2 , resting LVEF 70 ± 7%, 41% hypertension and 0% diabetes with no difference between TTS and controls. TTS had higher resting (140 ± 22 vs 123 ± 19 mmHg, p=0.049) and peak (187 ± 17 vs 171 ± 15 mmHg, p= 0.018) systolic blood pressure. While the early HMR and WR were similar, the late HMR was significantly lower in the TTS group (Figure). Conclusions: Women with a history of TTS have lower late HMR but similar WR, suggesting neuronal dysfunction in response to sympathetic challenge persists long after recovery from TTS event. Further analysis of catecholamine levels and central nervous system neural pathways will explore the mechanism of dysregulation.

Abstract 17680: MIBG Myocardial Scintigraphy is Useful for Predicting CTRCD Caused by Trastuzumab

Introduction: Trastuzumab is known to reduce the mortality rate, recurrence rate, and metastasis rate in Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer patients, and it is recommended to administer it for 12 months to all early-stage HER2-positive breast cancer patients. However, trastuzumab administration can lead to Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). The guidelines suggest that regular echocardiography every 3 months is useful for early detection of CTRCD, but there are no tests available to predict it before its onset.The purpose of this study is to determine whether cardiac sympathetic nerve evaluation using MIBG myocardial scintigraphy before trastuzumab administration can predict the development of CTRCD three months after administration. Methods: MIBG myocardial scintigraphy was performed before trastuzumab administration in 35 HER2-positive breast cancer patients, and cardiac function assessment was conducted using echocardiography before administration, at 1 month, and at 3 months. Simultaneously, NT-proBNP and troponin levels were measured. CTRCD was defined as a decrease in global longitudinal strain (GLS) of 10% or more from before administration at the 3-month follow-up. Results: Anthracycline and trastuzumab regimens were used in 21 patients (60%). CTRCD occurred in 17 patients at the 3-month follow-up. There were no significant differences in age or previous medication between the CTRCD group and the non-CTRCD group, but the early H/M ratio in MIBG myocardial scintigraphy was significantly lower in the CTRCD group (2.77±0.36) compared to the non-CTRCD group (3.10±0.36) (p&lt;0.01). There were no significant differences in the delay H/M ratio or washout rate. None of the echocardiographic parameters, NT-proBNP levels, or troponin levels showed significant differences and did not become predictive factors. Conclusions: MIBG myocardial scintigraphy is useful for predicting CTRCD caused by trastuzumab. Preclinical studies have suggested that HER2 transactivation from β-adrenergic receptors in the myocardium confers cardioprotection. Suppression of HER2 signaling during cardiac sympathetic nerve dysfunction potentially contributes to the development of CTRCD.

Dynamic contrast-enhanced ultrasonography with sonazoid predicts microvascular invasion in early-stage hepatocellular carcinoma.

Microvascular invasion (MVI) is an independent risk factor for the early recurrence and poor survival of hepatocellular carcinoma (HCC). This study aims to investigate the potential clinical value of dynamic contrast-enhanced ultrasound (DCE-ultrasound)-Sonazoid in pre-operatively assessing MVI in HCC. This single centre prospective study included 140 patients with histopathologically confirmed single HCC lesions. Patients were classified according to the post-operative pathological information presence of MVI: MVI+ group (n = 32) and MVI- group (n = 108). All patients underwent DCE-ultrasound within 1 week before surgery. The quantitative perfusion parameters of HCC lesions, margins of HCC lesions, and distal liver parenchyma were obtained and analyzed. Clinicopathological (serum alpha-fetoprotein, Des-gamma-carboxyprothrombin, and pathological grade) and grayscale imaging features (tumor size) were significantly different between the MVI+ and MVI- groups (p < 0.05). Further quantitative analysis showed that when comparing the MVI+ and MVI- groups, half-decrease time and wash-out rate of HCC lesions and peak enhancement in the arterial phase of difference between the margin area of HCC and distal liver parenchyma were significantly different (p = 0.045, p = 0.035, and p = 0.023, respectively). Combining the above three quantitative parameters, the accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value were 69.3% (97/140), 37.8% (17/45), 84.3% (80/95), 53.1% (17/32), 74.1% (80/108), respectively. DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions. DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.

Role of 99mTc-sestamibi Scintimammography in Predicting Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Prospective Study.

Neoadjuvant chemotherapy (NACT) is the first line of management for locally advanced breast cancer (LABC). However, chemoresistance is prevalent in 18%-50% of the cases. One of the important and most studied causes of chemoresistance is P-glycoprotein (Pgp) expression. 99mTc-sestamibi scintimammography may serve as a useful imaging tool to predict Pgp expression, thereby response to NACT. The aim was to study the role of 99mTc-sestamibi scintimammography in predicting response to NACT in treatment-naive, biopsy-proven LABC patients. 99mTc-sestamibi scintimammography (early and delayed images) was performed on a total of 34 patients. Eight patients were lost to follow-up, and only 26 (25 females and 1 male) patients were available for final analysis, with a mean age of 49.7 ± 10.7 years. 99mTc-sestamibi washout rate (WOR) (%) and T/B buildup were calculated. Pre-NACT and Post-NACT tumor sizes were measured clinically, and a % decrease in tumor size was calculated. The WOR and T/B buildup values were correlated with the % decrease in tumor size. We found a statistically significant negative correlation between WOR (%) and % decrease in tumor size and a statistically significant positive correlation between T/B buildup and % decrease in tumor size. Furthermore, we found a positive correlation between the early T/B ratio and the Ki-67 index (P = 0.22). Early categorization of responders and nonresponders can help in optimal therapy planning. 99mTc-sestamibi scintimammography can serve as an imaging marker for Pgp expression, thereby predicting clinical response to NACT in LABC patients. Further studies with larger sample sizes are warranted to consolidate the above findings.

Contrast-enhanced ultrasonography of the thyroid gland in healthy dogs, hypothyroid dogs and dogs with non-thyroidal illness

Diagnosis of canine hypothyroidism remains challenging, as non-thyroidal illness (NTI)-syndrome and medical treatment can influence thyroid hormone concentrations. Conventional ultrasound may give additional hints, however high interobserver variability has been described. Contrast-enhanced ultrasound (CEUS) allows detection of changes in tissue perfusion. The purpose of the present study was to assess the possible diagnostic value of CEUS regarding diagnosis of hypothyroidism. CEUS of the thyroid gland was performed in 52 healthy dogs, 16 hypothyroid dogs, and 20 NTI patients. The following perfusion parameters were calculated: Thyroid/carotid artery (TG/CA) ratios for peak enhancement (PE) and area under the curve (AUC), time to peak (TTP) and wash-in and wash-out rates (WiR, WoR) of the thyroid gland. Impact of sedation on perfusion parameters was investigated in 8 calm healthy dogs which were examined before and after sedation using midazolam and butorphanol. Significantly higher median TG/CA ratios for PE were detected for the left and right thyroid lobe in dogs with hypothyroidism (0.97/0.96) compared to healthy dogs (0.85/0.85) and dogs with NTI (0.84/0.84). AUCs were also significantly increased in hypothyroid dogs when compared to other groups. Dogs with NTI showed significantly lower WiR and WoR compared to other groups. Values for TTP were not significantly different between groups. Sedation had only impact on results of TTP which was significantly prolonged in sedated dogs. In conclusion, CEUS of the thyroid gland can provide an additional tool for diagnosis of hypothyroidism in dogs and support its differentiation from NTI. Sedation has limited impact on CEUS results.

Tumour status prediction by means of carbon-ion beam irradiation: comparison of washout rates between in-beam PET and DCE-MRI in rats

Objective. Tumour response to radiation therapy appears as changes in tumour vascular condition. There are several methods for analysing tumour blood circulatory changes one of which is dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), but there is no method that can observe the tumour vascular condition and physiological changes at the site of radiation therapy. Positron emission tomography (PET) has been applied for treatment verification in charged particle therapy, which is based on the detection of positron emitters produced through nuclear fragmentation reactions in a patient’s body. However, the produced positron emitters are washed out biologically depending on the tumour vascular condition. This means that measuring the biological washout rate may allow evaluation of the tumour radiation response, in a similar manner to DCE-MRI. Therefore, this study compared the washout rates in rats between in-beam PET during 12C ion beam irradiation and DCE-MRI. Approach. Different vascular conditions of the tumour model were prepared for six nude rats. The tumour of each nude rat was irradiated by a 12C ion beam with simultaneous in-beam PET measurement. In 10–12 h, the DCE-MRI experiment was performed for the same six nude rats. The biological washout rate of the produced positron emitters (k 2,1st) and the MRI contrast agent (k 2a) were derived using the single tissue compartment model. Main results. A linear correlation was observed between k 2,1st and k 2a, and they were inversely related to fractional necrotic volume. Significance. This is the first animal study which confirmed the biological washout rate of in-beam PET correlates closely with tumour vascular condition measured with the MRI contrast agent administrated intravenously.

Effect of chemostat turnover rate and select antibiotics on Salmonella Typhimurium in the presence of porcine gastrointestinal tract bacteria

The effect of select antibiotics on Salmonella Typhimurium DT104 persistence in a porcine cecal continuous flow culture was examined under two different washout rates. Porcine continuous flow cultures were conducted in the presence or absence of Gram-positive antibiotic carbadox. Carbadox eliminated chemostat anaerobes culturable on Brucella agar under 24 h turnover conditions, allowing Salmonella Typhimurium to persist for 15 days. Decreasing the culture dilution rate from a 24 to 48 h turnover time enabled Salmonella Typhimurium to maintain higher population levels more reflective of the theoretical washout rate when grown with than without added carbadox. This observation suggests that at the slower growth rate the presence of carbadox was antagonistic to the indigenous competitive exclusion potential of the mixed microbial population.

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.

Individualisation of radiation protection recommendations for patients treated with [177Lu]Lu-DOTA-TATE

BackgroundAs for any other nuclear medicine treatment, patients treated with [177Lu]Lu-DOTA-TATE should be given some radiation protection recommendations after being discharged to limit the dose received by family members and public. The restriction periods will depend on the remaining activity at the time of discharge, the washout rate and patients’ personal conditions. The activity in patients’ whole-body follows a bi-exponential behaviour. At the time of discharge only the first part of the time-activity curve is known. However, the second phase of the bi-exponential curve should be known to individualize the time of restrictions. The main purpose of this prospective study was to establish a simple method for calculating the restriction periods based on measurements taken before discharge.MethodsThe whole-body time-activity curve was calculated for 20 patients from dose-rate measurements performed during the first week post-administration. An effective decay time T_{{{text{eff}}}}^{6,24} was calculated from a mono-exponential fit performed with the 6 h and 24 h measurements and compared with the effective decay time T_{{{text{eff}}}}^{24,48,168} obtained from the mono-exponential fit performed with the 24 h, 48 h and 168 h measurements. The differences between them were calculated and the 95th percentile of these differences was used as a correction factor for T_{{{text{eff}}}}^{6,24}. A modified effective decay T_{{{text{eff}},{text{ mod}}}}^{6,24} was obtained by adding the correction factor to T_{{{text{eff}}}}^{6,24} and the restriction periods for each patient was calculated. The whole body activity washout between the first and the fourth treatment cycles of 16 patients was also compared.ResultsThe comparison of the whole-body activity curves between the first and the fourth cycle of the treatment for 16 patients would indicate that the recommendations on radiation protection determined from the first cycle could reasonably be used for the remaining cycles in most patients. The values of T_{{{text{eff}}}}^{6,24} and T_{{{text{eff}}}}^{24,48,168} obtained for the 20 patients were significantly different. The 95th percentile of the differences between T_{{{text{eff}}}}^{6,24} and T_{{{text{eff}}}}^{24,48,168} was 46 h, which is thus the time to be added to T_{{{text{eff}}}}^{6,24} so as to determine the restriction periods.ConclusionsThe proposed method makes it possible to calculate the restriction periods for patients treated with [177Lu]Lu-DOTA-TATE before they leave the hospital in a conservative and individualized way.

Can the Gleason score be predicted in patients with prostate cancer? A dynamic contrast-enhanced MRI, (68)Ga-PSMA PET/CT, PSA, and PSA-density comparison study.

The present study aims to evaluate whether perfusion parameters in prostate magnetic resonance imaging (MRI), (68)Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), prostate-specific antigen (PSA), and PSA density can be used to predict the lesion grade in patients with prostate cancer (PCa). The study included a total of 137 PCa cases in which 12-quadrant transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed, the Gleason score (GS) was determined, and pre-biopsy multiparametric prostate MRI and (68)Ga-PSMA PET/CT examinations were undertaken. The patient population was evaluated in three groups according to the GS: (1) low risk; (2) intermediate risk; (3) high risk. The PSA, PSA density, pre-TRUSBx (68)Ga-PSMA PET/CT maximum standardized uptake value (SUVmax), perfusion MRI parameters [maximum enhancement, maximum relative enhancement, T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1)] were retrospectively evaluated. There was no significant difference between the three groups in relation to the PSA, PSA density, and (68)Ga-PSMA PET/CT SUVmax (P > 0.05). However, the values of maximum enhancement, maximum relative enhancement (%), T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1) significantly differed among the groups. A moderate positive correlation was found among the prostate volume, PSA (r = 0.490), and (68)Ga-PSMA SUVmax (r = 0.322) in the patients. The wash-out rate (s-1) and wash-in rate (s-1) had the best diagnostic test performance (area under the curve: 89.1% and 78.4%, respectively). No significant correlation was found between the (68)Ga-PSMA PET/CT SUVmax and the GS. The wash-out rate was more successful in estimating the pretreatment GS than the (68)Ga-PSMA PET/CT SUVmax.

Pressure Clamping During Ocular Perfusions Drives Nitric Oxide-Mediated Washout.

The aim of this study was to test the hypothesis that nitric oxide (NO) mediates a pressure-dependent, negative feedback loop that maintains conventional outflow homeostasis and thus IOP. If true, holding pressure during ocular perfusions will result in uncontrolled production of NO, hyper-relaxation of the trabecular meshwork, and washout. Paired porcine eyes were perfused at constant pressure of 15 mmHg. After 1 hour acclimatization, one eye was exchanged with N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester, monohydrochloride (L-NAME) (50 µm) and the contralateral eye with DBG, and perfused for 3 hours. In a separate group, one eye was exchanged with DETA-NO (100 nM) and the other with DBG and perfused for 30 minutes. Changes in conventional outflow tissue function and morphology were monitored. Control eyes exhibited a washout rate of 15% (P = 0.0026), whereas eyes perfused with L-NAME showed a 10% decrease in outflow facility from baseline over 3 hours (P < 0.01); with nitrite levels in effluent positively correlating with time and facility. Compared with L-NAME-treated eyes, significant morphological changes in control eyes included increased distal vessel size, number of giant vacuoles, and juxtacanalicular tissue separation from the angular aqueous plexi (P < 0.05). For 30-minute perfusions, control eyes showed a washout rate of 11% (P = 0.075), whereas DETA-NO-treated eyes showed an increased washout rate of 33% from baseline (P < 0.005). Compared with control eyes, significant morphological changes in DETA-NO-treated eyes also included increased distal vessel size, number of giant vacuoles and juxtacanalicular tissue separation (P < 0.05). Uncontrolled NO production is responsible for washout during perfusions of nonhuman eyes where pressure is clamped.

Cardiac sympathetic activity and relationship to cardiac events and left ventricular reverse remodeling in patients with non-ischemic dilated cardiomyopathy.

Delayed heart-to-mediastinum ratio (HMR) has been associated with catecholamine levels and contractile reserve in dilated cardiomyopathy (DCM); however, there is scant evidence regarding the association between cardiac sympathetic activity and left ventricular reverse remodeling (LV-RR). We calculated the 123I-metaiodobenzylguanidine (123I-mIBG) HMR and washout rate (WR) in patients with DCM and investigated their associations with LV-RR. From April 2003 to January 2020, in 120 patients with DCM who underwent 123I-mIBG scintigraphy. 66 patients undergoing follow-up echo and taking a beta-blocker from baseline were examined the relationship between 123I-mIBG and LV-RR. After that, this prognostic value for composite cardiac events was evaluated in the entire 120 patients. In LV-RR analysis, patients were 50.4 ± 12.2years, with a mean left ventricular ejection fraction of 28.6%. Of 66 patients, 28 (42.4%) achieved LV-RR. Multiple logistic regression analysis of LV-RR revealed that not delayed HMR but the WR (cutoff value: 13.5%) was an independent predictor of LV-RR (odds ratio 6.514, p = 0.002). In the analysis for composite cardiac events, even though WR itself does not have the prognostic capacity, Kaplan-Meier survival curves divided by the cutoff value (delayed HMR = 2.0, WR = 13.5) showed that delayed HMR and WR values enabled the stratification of high-risk patients (log-rank p < 0.001). The 123I-mIBG WR was associated with the prevalence of LV-RR in patients taking 100% of beta-blockers and 98.5% of renin-angiotensin system inhibitors. Reflecting the contractile reserve, the combined assessment of the delayed HMR and WR could be used to further precisely stratify the patients with DCM.

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 &lt;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 &gt;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.