Quantitative Dual-Energy CT Image Guidance for Thermochemical Ablation: In Vivo Results in the Rabbit VX2 Model.

PURPOSE: To evaluate the feasibility of using dual-energy computed tomography (CT) and theranostic cesium hydroxide (CsOH) for image guidance of thermochemical ablation (TCA) in a rabbit VX2 tumor model. MATERIALS AND METHODS: In vivo experiments were performed on New Zealand white rabbits, where VX2 tumor fragments (0.3 mL) were inoculated into the right and left flanks (n = 16 rabbits, 32 tumors). Catheters were placed in the approximate center of 1- to 2-cm diameter tumors under ultrasound guidance. TCA was delivered in 1 of 3 treatment groups: untreated control, 5-M TCA, or 10-M TCA. The TCA base reagent was doped with 250-mM CsOH. Dual-energy CT was performed before and after TCA. Cesium (CS)-specific images were postprocessed on the basis of previous phantom calibrations to determine Cs concentration. Line profiles were drawn through the ablation center. Twenty-four hours after TCA, subjects were euthanized, and the resulting damage was evaluated with histopathology. RESULTS: Cs was detected in 100% of treated tumors (n = 21). Line profiles indicated highest concentrations at the injection site and decreased concentrations at the tumor margins, with no Cs detected beyond the ablation zone. The maximum detected Cs concentration ranged from 14.39 to 137.33 mM. A dose-dependent trend in tissue necrosis was demonstrated between the 10-M TCA and 5-M TCA treatment groups (P = .0005) and untreated controls (P = .0089). CONCLUSIONS: Dual-energy CT provided image guidance for delivery, localization, and quantification of TCA in the rabbit VX2 model.

Collagen/kerateine multi-protein hydrogels as a thermally stable extracellular matrix for 3D in vitro models.

Objective: To determine whether the addition of kerateine (reduced keratin) in rat tail collagen type I hydrogels increases thermal stability and changes material properties and supports cell growth for use in cellular hyperthermia studies for tumor treatment.Methods: Collagen type I extracted from rat tail tendon was combined with kerateine extracted from human hair fibers. Thermal, mechanical, and biocompatibility properties and cell behavior was assessed and compared to 100% collagen type I hydrogels to demonstrate their utility as a tissue model for 3D in vitro testing.Results: A combination (i.e., containing both collagen 'C/KNT') hydrogel was more thermally stable than pure collagen hydrogels and resisted thermal degradation when incubated at a hyperthermic temperature of 47°C for heating durations up to 60 min with a higher melting temperature measured by DSC. An increase in the storage modulus was only observed with an increased collagen concentration rather than an increased KTN concentration; however, a change in ECM structure was observed with greater fiber alignment and width with an increase in KTN concentration. The C/KTN hydrogels, specifically 50/50 C/KTN hydrogels, also supported the growth and of fibroblasts and MDA-MB-231 breast cancer cells similar to those seeded in 100% collagen hydrogels.Conclusion: This multi-protein C/KTN hydrogel shows promise for future studies involving thermal stress studies without compromising the 3D ECM environment or cell growth.

Distinguishing Non-Small Cell Lung Cancer Subtypes in Fine Needle Aspiration Biopsies by Desorption Electrospray Ionization Mass Spectrometry Imaging.

BACKGROUND: Distinguishing adenocarcinoma and squamous cell carcinoma subtypes of non-small cell lung cancers is critical to patient care. Preoperative minimally-invasive biopsy techniques, such as fine needle aspiration (FNA), are increasingly used for lung cancer diagnosis and subtyping. Yet, histologic distinction of lung cancer subtypes in FNA material can be challenging. Here, we evaluated the usefulness of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to diagnose and differentiate lung cancer subtypes in tissues and FNA samples. METHODS: DESI-MSI was used to analyze 22 normal, 26 adenocarcinoma, and 25 squamous cell carcinoma lung tissues. Mass spectra obtained from the tissue sections were used to generate and validate statistical classifiers for lung cancer diagnosis and subtyping. Classifiers were then tested on DESI-MSI data collected from 16 clinical FNA samples prospectively collected from 8 patients undergoing interventional radiology guided FNA. RESULTS: Various metabolites and lipid species were detected in the mass spectra obtained from lung tissues. The classifiers generated from tissue sections yielded 100% accuracy, 100% sensitivity, and 100% specificity for lung cancer diagnosis, and 73.5% accuracy for lung cancer subtyping for the training set of tissues, per-patient. On the validation set of tissues, 100% accuracy for lung cancer diagnosis and 94.1% accuracy for lung cancer subtyping were achieved. When tested on the FNA samples, 100% diagnostic accuracy and 87.5% accuracy on subtyping were achieved per-slide. CONCLUSIONS: DESI-MSI can be useful as an ancillary technique to conventional cytopathology for diagnosis and subtyping of non-small cell lung cancers.

Application of Trifluoroacetic Acid as a Theranostic Agent for Chemical Ablation of Solid Tissue.

PURPOSE: To evaluate trifluoroacetic acid (TFA) as a theranostic chemical ablation agent and determine the efficacy of TFA for both noninvasive imaging and tissue destruction. MATERIALS AND METHODS: Fluorine-19 magnetic resonance imaging (19F-MRI) was optimized at 7 T using a custom-built volume coil. Fluorine images were acquired with both rapid acquisition with relaxation enhancement and balanced steady-state free precession (bSSFP) sequences with varying parameters to determine the optimal sequence for TFA. The theranostic efficacy of chemical ablation was examined by injecting TFA (100 µL; 0.25, 0.5, 1.0, and 2.0M) into ex vivo porcine liver. 19F and proton MRI were acquired and superimposed to visualize distribution of TFA in tissue and quantify sensitivity. Tissue damage was evaluated with gross examination, histology, and fluorescence microscopy. RESULTS: The optimal 19F-MRI sequence was found to be bSSFP with a repetition time of 2.5 ms and flip angle of 70°. The minimum imageable TFA concentration was determined to be 6.7 ± 0.5 mM per minute of scan time (0.63×0.63×5.00 mm voxel), and real-time imaging (temporal resolution of at least 1 s-1) was achieved with 2M TFA both in vitro and in ex vivo tissue. TFA successfully coagulated tissue, and damage was locally confined. In addition to hepatic cord disruption, cytoskeletal collapse and chromatin clumping were observed in severely damaged areas in tissues treated with 0.5M or higher TFA concentrations. CONCLUSIONS: TFA was determined to be a theranostic agent for chemical ablation of solid tissue. Ablation was both efficacious and imageable in ex vivo healthy tissue, even at low concentrations or with high temporal resolution.

Mathematical modeling of mass and energy transport for thermoembolization.

Background: Thermoembolization presents a unique treatment alternative for patients diagnosed with hepatocellular carcinoma. The approach delivers a reagent that undergoes an exothermic chemical reaction and combines the benefits of embolic as well as thermal- and chemical-ablative therapy modalities. The target tissue and vascular bed are subjected to simultaneous hyperthermia, ischemia, and chemical denaturation in a single procedure. To guide optimal delivery, we developed a mathematical model for understanding the competing diffusive and convective effects observed in thermoembolization delivery protocols.Methods: A mixture theory formulation was used to mathematically model thermoembolization as chemically reacting transport of an electrophile, dichloroacetyl chloride (DCACl), within porous living tissue. Mass and energy transport of each relevant constituent are considered. Specifically, DCACl is injected into the vessels and exothermically reacts with water in the blood or tissue to form dichloroacetic acid and hydrochloric acid. Neutralization reactions are assumed instantaneous in this approach. We validated the mathematical model predictions of temperature using MR thermometry of the thermoembolization procedure performed in ex vivo kidney.Results: Mathematical modeling predictions of tissue death were highly dependent on the vascular geometry, injection pressure, and intrinsic amount of exothermic energy released from the chemical species, and were able to recapitulate the temperature distributions observed in MR thermometry.Conclusion: These efforts present a first step toward formalizing a mathematical model for thermoembolization and are promising for providing insight for delivery protocol optimization. While our approach captured the observed experimental temperature measurements, larger-scale experimental validation is needed to prioritize additional model complexity and fidelity.

Heating technology for malignant tumors: a review.

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 °C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.

Dual-Energy CT: Lower Limits of Iodine Detection and Quantification.

Background Assessments of the quantitative limitations among the six commercially available dual-energy (DE) CT acquisition schemes used by major CT manufacturers could aid researchers looking to use iodine quantification as an imaging biomarker. Purpose To determine the limits of detection and quantification of DE CT in phantoms by comparing rapid peak kilovoltage switching, dual-source, split-filter, and dual-layer detector systems in six different scanners. Materials and Methods Seven 50-mL iohexol solutions were used, with concentrations of 0.03-2.0 mg iodine per milliliter. The solutions and water sample were scanned five times each in two phantoms (small, 20-cm diameter; large, 30 × 40-cm diameter) with six DE CT systems and a total of 10 peak kilovoltage settings or combinations. Iodine maps were created, and the mean iodine signal in each sample was recorded. The limit of blank (LOB) was defined as the upper limit of the 95% confidence interval of the water sample. The limit of detection (LOD) was defined as the concentration with a 95% chance of having a signal above the LOB. The limit of quantification (LOQ) was defined as the lowest concentration where the coefficient of variation was less than 20%. Results The LOD range was 0.021-0.26 mg/mL in the small phantom and 0.026-0.55 mg/mL in the large phantom. The LOQ range was 0.07-0.50 mg/mL in the small phantom and 0.20-1.0 mg/mL in the large phantom. The dual-source and rapid peak kilovoltage switching systems had the lowest LODs, and the dual-layer detector systems had the highest LODs. Conclusion The iodine limit of detection using dual-energy CT systems varied with scanner and phantom size, but all systems depicted iodine in the small and large phantoms at or below 0.3 and 0.5 mg/mL, respectively, and enabled quantification at concentrations of 0.5 and 1.0 mg/mL, respectively. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Hindman in this issue.

On the Need for a Taxonomy for Interventional Radiology: Initiating Dialogue for the Future.

OBJECTIVE: Interventional radiology (IR) needs comprehensive structure. The reactive structure of the past is strategically unwise for long-term growth of IR. CONCLUSION: IR needs a structured approach to move forward most effectively. A preliminary taxonomic scaffold is put forth and critically analyzed to illustrate new areas of research for the field, to identify new opportunities for growth, and to serve as a starting point for future discussion.

Temperature mapping of exothermic in situ chemistry: imaging of thermoembolization via MR.

Purpose: MR temperature imaging (MRTI) was employed for visualizing the spatiotemporal evolution of the exotherm of thermoembolization, an investigative transarterial treatment for solid tumors. Materials and methods: Five explanted kidneys were injected with thermoembolic solutions, and monitored by MRTI. In three nonselective experiments, 5 ml of 4 mol/l dichloroacetyl chloride (DCA-Cl) solution in a hydrocarbon vehicle was injected via the main renal artery. For two of these three, MRTI temperature data were compared to fiber optic thermal probes. Another two kidneys received selective injections, treating only portions of the kidneys with 1 ml of 2 mol/l DCA-Cl. MRTI data were acquired and compared to changes in pre- and post-injection CT. Specimens were bisected and photographed for gross pathology 24 h post-procedure. Results: MRTI temperature estimates were within ±1 °C of the probes. In experiments without probes, MRTI measured increases of 30 °C. Some regions had not reached peak temperature by the end of the >18 min acquisition. MRTI indicated the initial heating occurred in the renal cortex, gradually spreading more proximally toward the main renal artery. Gross pathology showed the nonselective injection denatured the entire kidney whereas in the selective injections, only the treated territory was coagulated. Conclusion: The spatiotemporal evolution of thermoembolization was visualized for the first time using noninvasive MRTI, providing unique insight into the thermodynamics of thermoembolization. Précis Thermoembolization is being investigated as a novel transarterial treatment. In order to begin to characterize delivery of this novel treatment modality and aid translation from the laboratory to patients, we employ MR temperature imaging to visualize the spatiotemporal distribution of temperature from thermoembolization in ex vivo tissue.

A molecular dynamics approach towards evaluating osmotic and thermal stress in the extracellular environment.

OBJECTIVE: A molecular dynamics approach to understanding fundamental mechanisms of combined thermal and osmotic stress induced by thermochemical ablation (TCA) is presented. METHODS: Structural models of fibronectin and fibronectin bound to its integrin receptor provide idealized models for the effects of thermal and osmotic stress in the extracellular matrix. Fibronectin binding to integrin is known to facilitate cell survival. The extracellular environment produced by TCA at the lesion boundary was modelled at 37 °C and 43 °C with added sodium chloride (NaCl) concentrations (0, 40, 80, 160, and 320 mM). Atomistic simulations of solvated proteins were performed using the GROMOS96 force field and TIP3P water model. Computational results were compared with the results of viability studies of human hepatocellular carcinoma (HCC) cell lines HepG2 and Hep3B under matching thermal and osmotic experimental conditions. RESULTS: Cell viability was inversely correlated with hyperthermal and hyperosmotic stresses. Added NaCl concentrations were correlated with a root mean square fluctuation increase of the fibronectin arginylglycylaspartic acid (RGD) binding domain. Computed interaction coefficients demonstrate preferential hydration of the protein model and are correlated with salt-induced strengthening of hydrophobic interactions. Under the combined hyperthermal and hyperosmotic stress conditions (43 °C and 320 mM added NaCl), the free energy change required for fibronectin binding to integrin was less favorable than that for binding under control conditions (37 °C and 0 mM added NaCl). CONCLUSION: Results quantify multiple measures of structural changes as a function of temperature increase and addition of NaCl to the solution. Correlations between cell viability and stability measures suggest that protein aggregates, non-functional proteins, and less favorable cell attachment conditions have a role in TCA-induced cell stress.

Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs.

OBJECTIVE: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. METHODS: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). RESULTS: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. CONCLUSION: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.

Cost effectiveness of radioembolization compared with conventional transarterial chemoembolization for treatment of hepatocellular carcinoma.

PURPOSE: To assess cost effectiveness of radioembolization versus conventional transarterial chemoembolization. MATERIALS AND METHODS: The cost of radioembolization versus conventional transarterial chemoembolization was determined based on Medicare reimbursements. Three patient subgroups were defined based on the Barcelona Clinic Liver Cancer (BCLC) classification system (A, B, or C). Efficacy and safety outcomes after each procedure were obtained from the literature. A Monte Carlo case-based simulation was designed for 60 months in 250 patients in each subgroup. Survival was calculated based on average survival from the literature and the Monte Carlo model. The primary outcome was the cost effectiveness of radioembolization over transarterial chemoembolization by considering calculated survival. RESULTS: The costs approached $17,000 for transarterial chemoembolization versus $31,000 or $48,000 for unilobar or bilobar radioembolization, respectively. Based on the simulation, median estimated survival was greater with transarterial chemoembolization than radioembolization in BCLC-A and BCLC-B subgroups (40 months vs 30 months and 23 months vs 16 months, respectively, P = .001). However, in the BCLC-C subgroup, survival was greater with radioembolization than transarterial chemoembolization (13 months vs 17 months, P = .001). The incremental cost-effectiveness ratio of radioembolization over transarterial chemoembolization in the BCLC-C subgroup was $360 per month. The results were dependent on bilobar versus unilobar radioembolization and the total number of radioembolization procedures. CONCLUSIONS: The model suggests radioembolization costs may be justified for patients with BCLC-C disease, whereas radioembolization may not be cost effective in patients with BCLC-A disease; however, many patients with BCLC-C disease have extensive disease precluding locoregional therapies. Secondary considerations may determine treatment choice in more borderline patients (BCLC-B disease) because there is no persistent survival benefit with radioembolization.

1D Thermoembolization Model Using CT Imaging Data for Porcine Liver.

Objective: Innovative therapies such as thermoembolization are expected to play an important role in improving care for patients with diseases such as hepatocellular carcinoma. Thermoembolization is a minimally invasive strategy that combines thermal ablation and embolization in a single procedure. This approach exploits an exothermic chemical reaction that occurs when an acid chloride is delivered via an endovascular route. However, comprehension of the complexities of the biophysics of thermoembolization is challenging. Mathematical models can aid in understanding such complex processes and assisting clinicians in making informed decisions. In this study, we used a Hagen-Poiseuille 1D blood flow model to predict the mass transport and possible embolization locations in a porcine hepatic artery. Method: The 1D flow model was used on imaging data of in-vivo embolization imaging data of three pigs. The hydrolysis time constant of acid chloride chemical reaction was optimized for each pig, and LOOCV method was used to test the model's predictive ability. Conclusion: This basic model provided a balanced accuracy rate of 66.8% for identifying the possible locations of damage in the hepatic artery. Use of the model provides an initial understanding of the vascular transport phenomena that are predicted to occur as a result of thermoembolization.

Dual mode single agent thermochemical ablation by simultaneous release of heat energy and acid: hydrolysis of electrophiles.

PURPOSE: This study aimed to investigate two readily available electrophilic reagents, acetyl chloride (AcCl), and acetic anhydride (Ac(2)O), for their potential in tissue ablation. MATERIALS AND METHODS: Reagents were diluted in diglyme as solutions up to 8 mol/L and tested in a gel phantom with NaOH solutions and ex vivo in porcine liver. Temperature, pH, and volume measurements were obtained. Infrared and gross pathological images were obtained in bisected specimens immediately after injection. RESULTS: AcCl was much more reactive than Ac(2)O and AcCl was therefore used in the tissue studies. Temperature increases of up to 37°C were noted in vitro and 30°C in ex vivo tissues using 4 mol/L AcCl solutions. Experiments at 8 mol/L were abandoned due to the extreme reactivity at this higher concentration. A change in pH of up to 4 log units was noted with 4 mol/L solutions of AcCl with slight recovery over time. Ablated volumes were consistently higher than injected volumes. CONCLUSIONS: Reaction of electrophiles in tissues shows promise as a new thermochemical ablation technique by means of only a single reagent. Further studies in this area are warranted.

Cellular and molecular mechanisms of hepatocellular carcinoma: an update.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor that accounts for ~80 % of all liver cancer cases worldwide. It is a multifactorial disease caused by a variety of risk factors and often develops in the background of underlying cirrhosis. A number of cellular phenomena, such as tumor microenvironment, inflammation, oxidative stress, and hypoxia act in concert with various molecular events to facilitate tumor initiation, progression, and metastasis. The emergence of microRNAs and molecular-targeted therapies adds a new dimension in our efforts to combat this deadly disease. Intense research in this multitude of areas has led to significant progress in our understanding of cellular processes and molecular mechanisms that occur during multistage events that lead to hepatocarcinogenesis. In this review, we discuss the current knowledge of HCC, focusing mainly on advances that have occurred during the past 5 years and on the development of novel therapeutics for liver cancer.

Quantitative dual-energy computed tomography with cesium as a novel contrast agent for localization of thermochemical ablation in phantoms and ex vivo models.

BACKGROUND: Thermochemical ablation (TCA) is a minimally invasive therapy under development for hepatocellular carcinoma. TCA simultaneously delivers an acid (acetic acid, AcOH) and base (sodium hydroxide, NaOH) directly into the tumor, where the acid/base chemical reaction produces an exotherm that induces local ablation. However, AcOH and NaOH are not radiopaque, making monitoring TCA delivery difficult. PURPOSE: We address the issue of image guidance for TCA by utilizing cesium hydroxide (CsOH) as a novel theranostic component of TCA that is detectable and quantifiable with dual-energy CT (DECT). MATERIALS AND METHODS: To quantify the minimum concentration of CsOH that can be positively identified by DECT, the limit of detection (LOD) was established in an elliptical phantom (Multi-Energy CT Quality Assurance Phantom, Kyoto Kagaku, Kyoto, Japan) with two DECT technologies: a dual-source system (SOMATOM Force, Siemens Healthineers, Forchheim, Germany) and a split-filter, single-source system (SOMATOM Edge, Siemens Healthineers). The dual-energy ratio (DER) and LOD of CsOH were determined for each system. Cesium concentration quantification accuracy was evaluated in a gelatin phantom before quantitative mapping was performed in ex vivo models. RESULTS: On the dual-source system, the DER and LOD were 2.94 and 1.36-mM CsOH, respectively. For the split-filter system, the DER and LOD were 1.41- and 6.11-mM CsOH, respectively. The signal on cesium maps in phantoms tracked linearly with concentration (R2  = 0.99) on both systems with an RMSE of 2.56 and 6.72 on the dual-source and split-filter system, respectively. In ex vivo models, CsOH was detected following delivery of TCA at all concentrations. CONCLUSIONS: DECT can be used to detect and quantify the concentration of cesium in phantom and ex vivo tissue models. When incorporated in TCA, CsOH performs as a theranostic agent for quantitative DECT image-guidance.

Vascularized Hepatocellular Carcinoma on a Chip to Control Chemoresistance through Cirrhosis, Inflammation and Metabolic Activity.

Understanding the effects of inflammation and cirrhosis on the regulation of drug metabolism during the progression of hepatocellular carcinoma (HCC) is critical for developing patient-specific treatment strategies. In this work, we created novel three-dimensional vascularized HCC-on-a-chips (HCCoC), composed of HCC, endothelial, stellate, and Kupffer cells tuned to mimic normal or cirrhotic liver stiffness. HCC inflammation was controlled by tuning Kupffer macrophage numbers, and the impact of cytochrome P450-3A4 (CYP3A4) was investigated by culturing HepG2 HCC cells transfected with CYP3A4 to upregulate expression from baseline. This model allowed for the simulation of chemotherapeutic delivery methods such as intravenous injection and transcatheter arterial chemoembolization (TACE). We showed that upregulation of metabolic activity, incorporation of cirrhosis and inflammation, increase vascular permeability due to upregulated inflammatory cytokines leading to significant variability in chemotherapeutic treatment efficacy. Specifically, we show that further modulation of CYP3A4 activity of HCC cells by TACE delivery of doxorubicin provides an additional improvement to treatment response and reduces chemotherapy-associated endothelial porosity increase. The HCCoCs were shown to have utility in uncovering the impact of the tumor microenvironment (TME) during cancer progression on vascular properties, tumor response to therapeutics, and drug delivery strategies.

Concentration and volume effects in thermochemical ablation in vivo: results in a porcine model.

PURPOSE: To explore the effects of volume and concentration in thermochemical ablation using an in vivo porcine model. METHODS: Twelve swine 60-75 kg were used in this institutionally approved study. A needle design prototype coaxial device for reagent injections and a thermocouple were inserted into surgically exposed liver. Simultaneously, an acid and base (acetic acid and NaOH) were injected at 4 mL/min based on a 3 × 3 matrix with concentration (5, 10, and 15 mol/L) and volume on the axes (total volumes of 1, 2, and 4 mL). Three animals (centre grid position) strengthened the statistical analysis. Each animal received four identical injections (total 48). Temperatures and heart rate were recorded. Livers were formalin-fixed after sacrifice. After sectioning, coagulation zones were analysed by two observers. Area and slice thickness were used to calculate the volume, surface area, and sphericity for each treatment. RESULTS: Coagulation volumes ranged from 2.95 ± 0.29 to 14.72 ± 1.42 mL with a maximum of 18.3 mL. Highest peak temperature was 105°C with temperatures ranging 43.5 ± 2.6°C to 91.0 ± 6.5°C. There was no association between conditions and sphericity or heart rate. CONCLUSIONS: The method can be used successfully to ablate tissue in vivo. By neutralising acid in situ and releasing heat and a salt, this technique improves considerably upon the use of acetic acid used alone. Peak temperatures exceeded accepted coagulation thresholds even if the only mechanism operating was hyperthermia. Reagent concentrations and volumes increased the amount of the coagulum but not in a linear fashion.