The impact of thermally significant blood vessels in perfused tumor tissue on thermal dose distributions during thermal therapies

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

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An Analytical Evaluation of the Optimal Thermal Dose Delivery Parameters for Thermal Therapies

Heat Transfer: Volume 2 ◽

10.1115/ht2003-47361 ◽

2003 ◽

Cited By ~ 1

Author(s):

Kung-Shan Cheng ◽

Robert B. Roemer

Keyword(s):

Blood Flow ◽

Treatment Time ◽

Heating Time ◽

Treatment Temperature ◽

Thermal Dose ◽

Dose Delivery ◽

Thermal Therapies ◽

Initial Power ◽

High Treatment ◽

Optimal Heating

This study derives the first analytic solution for evaluating the optimal treatment parameters needed for delivering a desired thermal dose during thermal therapies consisting of a single heating pulse. Each treatment is divided into four time periods (two power-on and two power-off), and the thermal dose delivered during each of those periods is evaluated using the non-linear Sapareto and Dewey equation relating thermal dose to temperature and time. The results reveal that the thermal dose delivered during the second power-on period when T>43C (TD2) and the initial power-off period when T>43C (TD3) contribute the major portions of the total thermal dose needed for a successful treatment (taken as 240 CEM43°C), and that TD3 dominates for treatments with higher peak temperatures. For a fixed perfusion value, the analytical results show that once the maximum treatment temperature and the total thermal dose (e.g., 240 CEM43°C) are specified, then the required heating time and the applied power magnitude are uniquely determined. These are the optimal heating parameters since lower/higher values result in under-dosing/over-dosing of the treated region. It is also shown that higher maximum treatment temperatures result in shorter treatment times, and for each patient blood flow there is a maximum allowable temperature that can be used to reach the desired thermal dose. In addition, since TD2 and TD3 contribute most of the total thermal dose, and they are both significantly affected by the blood flow present for high treatment temperatures, these results show that perfusion effects must be considered when attempting to optimize high temperature thermal therapy treatments (no excess thermal dose delivered, minimum power applied and shortest treatment time attained).

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Тhe effect of cancer patients’ positioning accuracy during radiation therapy sessions using medical linear electron accelerators on the parameters of their individual 3D dose distribution

Doklady BGUIR ◽

10.35596/1729-7648-2020-18-7-31-39 ◽

2020 ◽

Vol 18 (7) ◽

pp. 31-39

Author(s):

M. N. Piatkevich ◽

E. V. Titovich ◽

G. V. Belkov

Keyword(s):

Radiation Therapy ◽

Radiation Treatment ◽

Malignant Tumors ◽

Rapid Development ◽

Treatment Session ◽

Malignant Neoplasms ◽

Horizontal Position ◽

Individual Dose ◽

Dose Distributions ◽

The Impact

Due to the rapid development and further improvement of radiation treatment technologies oncologists have an opportunity to precisely deliver individual dose distributions to the tumor, minimizing the doses obtained by critical organs and healthy structures. For the correct and successful application of these complex methods of radiation therapy, it was necessary to enforce the requirements for the technical and dosimetric parameters of the radiotherapy equipment. The purpose of the research is to determine the magnitude of the possible error for patients’ positioning during their radiotherapy treatments using medical linear accelerators by modeling the impact of the patient’s body on the treatment couch. To determine the values of a possible error, the authors have considered the design and characteristics of a typical treatment couch, developed a model of the “average” patient’s body (phantom), which allowed changing the load to the treatment couch with a step of 1 kg. The position parameters of treatment couches were determined for the main types of localization of radiation therapy for malignant tumors: head and neck tumors, breast tumors and pelvic tumors. Numerical values of the treatment coach deviations from prescribed horizontal position were experimentally established for a load from 40 to 180 kg for a treatment couch used at the N.N. Alexandrov National Cancer Centre of Belarus. Based on the obtained experimental data, the necessity to correct the patient's treatment conditions at the stage of treatment planning were confirmed in order to ensure the delivery accuracy of individual dose distributions as required by the radiation therapy protocols. Authors stated that an analysis of the dependence of the deviations in the dose delivered to the patients on the deviation of the radiotherapy table from its horizontal position should be carried out for each radiotherapy table used in clinical practice. The development and implementation of a mechanism that will allow considering this information when choosing the parameters of the patient’s treatment session and prescribing the dose for any localization of malignant neoplasms is needed.

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Minimum-Time Thermal Dose Control of Thermal Therapies

IEEE Transactions on Biomedical Engineering ◽

10.1109/tbme.2004.840471 ◽

2005 ◽

Vol 52 (2) ◽

pp. 191-200 ◽

Cited By ~ 30

Author(s):

D. Arora ◽

M. Skliar ◽

R.B. Roemer

Keyword(s):

Minimum Time ◽

Thermal Dose ◽

Thermal Therapies ◽

Dose Control

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The impact of magnetic field on blood vessels

2013 IEEE XXXIII International Scientific Conference Electronics and Nanotechnology (ELNANO) ◽

10.1109/elnano.2013.6552086 ◽

2013 ◽

Author(s):

M. M. Baran ◽

N. V. Kostevska ◽

V. P. Virchenko ◽

Y. S. Synekop ◽

A. I. Mukhomor

Keyword(s):

Magnetic Field ◽

Blood Vessels ◽

The Impact

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Modeling and Simulation on Heat Transfer in Blood Vessels Subject to a Transient Laser Irradiation

Journal of Heat Transfer ◽

10.1115/1.4045669 ◽

2020 ◽

Vol 142 (3) ◽

Author(s):

Xuelan Zhang ◽

Liancun Zheng ◽

Lin Liu ◽

Xinxin Zhang

Keyword(s):

Heat Transfer ◽

Blood Vessels ◽

Laser Irradiation ◽

Numerical Solutions ◽

Thermal Relaxation ◽

Initial Time ◽

Laser Exposure ◽

Conduction Model ◽

Heaviside Step Function ◽

The Impact

Abstract This paper investigates heat transfer of blood vessels subject to transient laser irradiation, where the irradiation is extremely short times and has high power. The modified Fourier heat conduction model (Cattaneo–Christov flux) and Heaviside step function are used in describing the thermal relaxation and temperature jump characteristics in initial time. A novel auxiliary function is introduced to avoid three-level discretization and temporal–spatial mixed derivative, and the numerical solutions are obtained by Crank–Nicolson alternating direction implicit (ADI) scheme. Results indicate that the temperature distributions in blood vessels strongly depend on the blood property, the laser exposure time, the blood flowrate (Reynolds number) and the thermal relaxation parameter. The isothermal curve exhibits asymmetric characteristics due to the impact of blood flow, and the higher blood velocity leads to more asymmetric isotherm and less uniform thermal distribution. Further, the heat-flux relaxation phenomenon is also captured, and its effect on blood temperature becomes more noticeable as blood flows downstream of blood vessels.

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Performance Assessment of Probe for Radio-Frequency Ablation

Volume 4 ◽

10.1115/ht-fed2004-56422 ◽

2004 ◽

Author(s):

Ashvinikumar V. Mudaliar ◽

Elaine P. Scott

Keyword(s):

Temperature Distribution ◽

Radio Frequency ◽

Tumor Tissue ◽

Healthy Tissue ◽

Lower Portion ◽

Distribution Data ◽

Thermal Dose ◽

Rf Ablation ◽

Ablation Therapy ◽

Tissue Region

Radio-frequency (RF) ablation is one of the most widely used methods for the treatment of hepatic malignancies. A finite element method (FEM) analysis was employed to determine the thermal dose delivered to the tumor/tissue region. We simulated heating within a RF probe implanted in generic tumor surrounded by healthy tissue using ANSYS. The 3-D model consists of a tumor / tissue region into which the RF probe is embedded inside the tumor. One-quarter symmetry was then invoked. The blood flow was modeled using Penne’s bio-heat transfer equation with differing perfusion rates between the healthy tissue and tumor volume based on literature values. The resulting temperature distribution throughout the region was determined over time. A program was written in Visual Basic to extract the temperature distribution data in the tumor/tissue region and calculate the thermal dose throughout the region. This was done by using a time–temperature Arrhenius relationship for chemical and physical rate process. Tissue necrosis is assumed complete when a thermal dose of one hour has been achieved at 43 °C. In the present study, the geometry of the electrode had a significant effect on the size of the volume of necrosis. It was found that the lower portion of the tumor did not receive the specified thermal dose relative to the upper portion of the tumor in single setting during the RF ablation therapy. This might be due to the Ni-Ti electrode, which protruded only from the top surface of the trocar. The effectiveness of the existing probe can be improved by having one more set of electrodes protruding out from the lower curved surface of the trocar. It was found that the modified probe significantly improved heating in the lower portion of tumor/tissue area, providing more symmetry between the upper and lower portion.

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SU-E-J-240: The Impact On Clinical Dose-Distributions When Using MR-Images Registered with Stereotactic CT-Images in Gamma Knife Radiosurgery

Medical Physics ◽

10.1118/1.4888293 ◽

2014 ◽

Vol 41 (6Part10) ◽

pp. 213-213

Author(s):

H Benmakhlouf ◽

T Wangerid ◽

T Kraepelien ◽

P Forander

Keyword(s):

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Ct Images ◽

Mr Images ◽

Dose Distributions ◽

Clinical Dose ◽

The Impact

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Immunolocalization of Heat Shock Protein after Fluid Percussive Brain Injury and Relationship to Breakdown of the Blood-Brain Barrier

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1993.14 ◽

1993 ◽

Vol 13 (1) ◽

pp. 116-124 ◽

Cited By ~ 68

Author(s):

Hirokazu Tanno ◽

Russ P. Nockels ◽

Lawrence H. Pitts ◽

Linda J. Noble

Keyword(s):

Brain Injury ◽

Head Injury ◽

Blood Vessels ◽

Blood Brain Barrier ◽

Time Course ◽

Cortical Layer ◽

Brain Barrier ◽

Impact Site ◽

Blood Brain ◽

The Impact

We have previously developed a model of mild, lateral fluid percussive head injury in the rat and demonstrated that although this injury produced minimal hemorrhage, breakdown of the blood–brain barrier was a prominent feature. The relationship between posttraumatic blood–brain barrier disruption and cellular injury is unclear. In the present study we examined the distribution and time course of expression of the stress protein HSP72 after brain injury and compared these findings with the known pattern of breakdown of the blood–brain barrier after a similar injury. Rats were subjected to a lateral fluid percussive brain injury (4.8–5.2 atm, 20 ms) and killed at 1, 3, and 6 h and 1,3, and 7 days after injury. HSP72-like immunoreactivity was evaluated in sections of brain at the light-microscopic level. The earliest expression of HSP72 occurred at 3 h postinjury and was restricted to neurons and glia in the cortex surrounding a necrotic area at the impact site. By 6 h, light immunostaining was also noted in the pia-arachnoid adjacent to the impact site and in certain blood vessels that coursed through the area of necrosis. Maximal immunostaining was observed by 24 h postinjury, and was primarily associated with the cortex immediately adjacent to the region of necrosis at the impact site. This region consisted of darkly immunostained neurons, glia, and blood vessels. Immunostaining within the region of necrosis was restricted to blood vessels. HSP72-like immunoreactivity was also noted in a limited number of neurons and glia in other brain regions, including the parasagittal cortex, deep cortical layer VI, and CA3 in the posterior hippocampus. Immunoreactive cells in these areas were not apparent until 24 h postinjury. By 7 days postinjury, HSP72-like immunoreactivity was minimal or absent in these injured brains and notable cell loss was apparent only in the impact site. This study demonstrates an early and pronounced expression of HSP72 at the impact site and a more delayed and less prominent expression of this protein in other regions of the brain. These findings parallel the temporal and regional pattern of breakdown of the blood–brain barrier after a similar head injury.

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