scholarly journals Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mrigendra B. Karmacharya ◽  
Laith R. Sultan ◽  
Stephen J. Hunt ◽  
Chandra M. Sehgal
Keyword(s):  
Hepatocellular Carcinoma ◽  
Blood Flow ◽  
Area Under The Curve ◽  
Ultrasound Treatment ◽  
Tumor Blood Flow ◽  
Future Studies ◽  
Peak Enhancement ◽  
Contrast Enhanced ◽  
Combined Use ◽  
Ultrasound Hyperthermia

AbstractThis study investigates the use of hydralazine to enhance ultrasound hyperthermia for the treatment of hepatocellular carcinoma (HCC) by minimizing flow-mediated heat loss from the tumor. Murine HCC tumors were treated with a continuous mode ultrasound with or without an intravenous administration of hydralazine (5 mg/kg). Tumor blood flow and blood vessels were evaluated by contrast-enhanced ultrasound (CEUS) imaging and histology, respectively. Hydralazine markedly enhanced ultrasound hyperthermia through the disruption of tumor blood flow in HCC. Ultrasound treatment with hydralazine significantly reduced peak enhancement (PE), perfusion index (PI), and area under the curve (AUC) of the CEUS time-intensity curves by 91.9 ± 0.9%, 95.7 ± 0.7%, and 96.6 ± 0.5%, compared to 71.4 ± 1.9%, 84.7 ± 1.1%, and 85.6 ± 0.7% respectively without hydralazine. Tumor temperature measurements showed that the cumulative thermal dose delivered by ultrasound treatment with hydralazine (170.8 ± 11.8 min) was significantly higher than that without hydralazine (137.7 ± 10.7 min). Histological assessment of the ultrasound-treated tumors showed that hydralazine injection formed larger hemorrhagic pools and increased tumor vessel dilation consistent with CEUS observations illustrating the augmentation of hyperthermic effects by hydralazine. In conclusion, we demonstrated that ultrasound hyperthermia can be enhanced significantly by hydralazine in murine HCC tumors by modulating tumor blood flow. Future studies demonstrating the safety of the combined use of ultrasound and hydralazine would enable the clinical translation of the proposed technique.

Potential application of dynamic contrast enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma

2021 ◽  
pp. 1-9
Author(s):  
Yi Dong ◽  
Yijie Qiu ◽  
Daohui Yang ◽  
Lingyun Yu ◽  
Dan Zuo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Area Under The Curve ◽  
Microvascular Invasion ◽  
Contrast Enhanced Ultrasound ◽  
Negative Group ◽  
Clinical Value ◽  
Positive Group ◽  
Quantitative Perfusion ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

OBJECTIVE: To investigate the clinical value of dynamic contrast enhanced ultrasound (D-CEUS) in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In this retrospective study, 16 patients with surgery and histopathologically proved HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n = 6) and MVI negative group (n = 10). Contrast enhanced ultrasound (CEUS) examinations were performed within a week before surgery. Dynamic analysis was performed by VueBox ® software (Bracco, Italy). Three regions of interests (ROIs) were set in the center of HCC lesions, at the margin of HCC lesions and in the surrounding liver parenchyma accordingly. Time intensity curves (TICs) were generated and quantitative perfusion parameters including WiR (wash-in rate), WoR (wash-out rate), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiPi (wash-in perfusion index) were obtained and analyzed. RESULTS: All of HCC lesions showed arterial hyperenhancement (100 %) and at the late phase as hypoenhancement (75 %) in CEUS. Among all CEUS quantitative parameters, the WiAUC and WoAUC were higher in MVI positive group than in MVI negative group in the center HCC lesions (P <  0.05), WiAUC, WoAUC and WiPI were higher in MVI positive group than in MVI negative group at the margin of HCC lesions. WiR and WoR were significant higher in MVI positive group. CONCLUSIONS: D-CEUS with quantitative perfusion analysis has potential clinical value in predicting the existence of MVI in HCC lesions.

Influence of ageing on quantitative contrast-enhanced ultrasound of the kidneys in healthy cats

2018 ◽  
Vol 182 (18) ◽  
pp. 515-515 ◽  
Author(s):  
Emmelie Stock ◽  
Dominique Paepe ◽  
Sylvie Daminet ◽  
Luc Duchateau ◽  
Jimmy H Saunders ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Area Under The Curve ◽  
Renal Perfusion ◽  
Urine Specific Gravity ◽  
Contrast Enhanced Ultrasound ◽  
Non Invasive ◽  
Peak Enhancement ◽  
Contrast Enhanced ◽  
Lower Blood ◽  
Invasive Evaluation

The degenerative effects of ageing on the kidneys have been extensively studied in humans. However, only recently interest has been focused on renal ageing in veterinary medicine. Contrast-enhanced ultrasound allows non-invasive evaluation of renal perfusion in conscious cats. Renal perfusion parameters were obtained in 43 healthy cats aged 1–16 years old, and the cats were divided in four age categories: 1–3 years, 3–6 years, 6–10 years and over 10 years. Routine renal parameters as serum creatinine, serum urea, urine-specific gravity, urinary protein:creatinine ratio and systolic blood pressure were also measured. No significant differences in any of the perfusion parameters were observed among the different age categories. A trend towards a lower peak enhancement and wash-in area under the curve with increasing age, suggestive for a lower blood volume, was detected when comparing the cats over 10 years old with the cats of 1–3 years old. Additionally, no significant age-effect was observed for the serum and urine parameters, whereas a higher blood pressure was observed in healthy cats over 10 years old.

scholarly journals Diagnostic Value of Imaging Methods in the Histological Four Grading of Hepatocellular Carcinoma

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 321 ◽  
Author(s):  
Feiqian Wang ◽  
Kazushi Numata ◽  
Masayuki Nakano ◽  
Mikiko Tanabe ◽  
Makoto Chuma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Area Under The Curve ◽  
Diagnostic System ◽  
Diagnostic Value ◽  
Imaging Method ◽  
Multicenter Studies ◽  
Diagnostic Efficacy ◽  
Portal Phase ◽  
Contrast Enhanced ◽  
Early Hcc

We attempted to establish an ultrasound (US) imaging-diagnostic system for histopathological grades of differentiation of hepatocellular carcinoma (HCC). We conducted a retrospective study of histopathologically confirmed 200 HCCs, classified as early (45 lesions), well- (31 lesions), moderately (68 lesions) or poorly differentiated (diff.) (56 lesions) HCCs. We performed grayscale US to estimate the presence/absence of halo and mosaic signs, Sonazoid contrast-enhanced US (CEUS) to determine vascularity (hypo/iso/hyper) of lesion in arterial and portal phase (PP), and echogenicity of lesion in post-vascular phase (PVP). All findings were of significance for the diagnosis of some (but not all) histological grades (p < 0.001–0.05). Combined findings with a relatively high diagnostic efficacy for early, poorly and moderately diff. HCC were a combination of absence of halo sign and isoechogenicity in PVP of CEUS (accuracy: 93.0%, AUC: 0.908), hypovascularity in PP (accuracy: 78.0%, area under the curve (AUC): 0.750), and a combination of isovascularity in PP and hypoechogenicity in PVP (accuracy: 75.0%, AUC: 0.739), respectively. On the other hand, neither any individual finding nor any combination of findings yielded an AUC of over 0.657 for the diagnosis of well-diff. HCC. Our study provides encouraging data on Sonazoid CEUS in the histological differential diagnosis of HCC, especially in early HCC, and the effectiveness of this imaging method should be further proved by prospective, large sample, multicenter studies.

A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of MN-029, a novel vascular disrupting agent (VDA), in patients (pts) with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3096-3096 ◽  
Author(s):  
A. D. Ricart ◽  
M. Cooney ◽  
J. Sarantopoulos ◽  
J. Brell ◽  
K. W. Locke ◽  
...  
Keyword(s):  
Blood Flow ◽  
Microtubule Assembly ◽  
Tumor Blood Flow ◽  
Post Dose ◽  
Temporary Reduction ◽  
Vascular Disrupting Agent ◽  
Dce Mri ◽  
Blood Flow Reduction ◽  
Contrast Enhanced ◽  
Tumor Types

3096 Background: MN-029 is a novel VDA that binds reversibly to the colchicine-binding site on tubulin and inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor endothelial cells (EC). Disruption of the tumor EC cytoskeleton ultimately leads to a temporary reduction in tumor blood flow. Methods: MN-029 is administered IV as a 10–20 min infusion, at 3-wk intervals in pts with advanced cancer. The study has followed an accelerated titration design, with intrapatient dose escalation. PD effects on tumor blood flow are evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: 28 pts were enrolled (13M/15F), median age 56 (range 35 - 76) and tumor types: colorectal (5), renal (5), hepatocellular (3), ovarian (2), melanoma (2), soft tissue sarcoma (2), carcinoid (2) and others (7). A total of 110 cycles of MN-029 were given, median 3/pt (range 1–20), over 9 dose levels (4, 8, 16, 24, 36, 54, 80, 120 and 180 mg/m2). Escalation proceeded until an initial dose-limiting toxicity (DLT) was observed in 1 pt in the 180 mg/m2 cohort, consisting of a reversible episode (3 hours post dose) of acute coronary ischemia (without sequelae and with preservation of myocardial function) probably due to coronary vasospasm. Therefore, this cohort was expanded to 6 pts, with no further DLTs observed. Common mild to moderate toxicities included nausea, vomiting (which appears dose-related), hypotension, fatigue and diarrhea. There was no significant myelotoxicity, stomatitis or alopecia. Seven pts had stable disease after 3 cycles, including 2 pts with carcinoid tumor (+21 cycles and +17 cycles). PK data generally indicated dose-related increases in Cmax and AUC values, although substantial inter-patient variability was observed. Tumor blood flow reduction assessed by DCE-MRI was recorded at 120 and 180 mg/m2, but not at 80 mg/m2. Conclusions: MN-029 produced reductions in tumor blood flow at doses that were well tolerated. Accrual continues at 225 mg/m2. [Supported in part by grants from MediciNova, Inc. and M01 RR-000080] [Table: see text]

Deep-Learning Based Analysis of Preoperative MRI Predicts Microvascular Invasion and Outcome in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Bao-Ye sun ◽  
Pei-Yi Gu ◽  
Ruo-Yu Guan ◽  
Cheng Zhou ◽  
Jian-Wei Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Deep Learning ◽  
Predictive Model ◽  
Clinical Outcomes ◽  
Area Under The Curve ◽  
Microvascular Invasion ◽  
Dce Mri ◽  
Preoperative Prediction ◽  
Model Combining ◽  
Contrast Enhanced

Abstract Background & Aims: Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC. Methods We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression. Results Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and AFP were independently associated with MVI: DL-MVI (odds ratio [OR]=35.738; 95% confidence interval [CI]: 14.027-91.056; p<0.001), AFP (OR=4.634, 95% CI: 2.576-8.336; p<0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824. Conclusions Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.

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