Pennes' bioheat equation vs. porous media approach in computer modeling of radiofrequency tumor ablation.

The objective of this study was to compare three different heat transfer models for radiofrequency ablation of in vivo liver tissue using a cooled electrode and three different voltage levels. The comparison was between the simplest but less realistic Pennes' equation and two porous media-based models, i.e. the Local Thermal Non-Equilibrium (LTNE) equations and Local Thermal Equilibrium (LTE) equation, both modified to take into account two-phase water vaporization (tissue and blood). Different blood volume fractions in liver were considered and the blood velocity was modeled to simulate a vascular network. Governing equations with the appropriate boundary conditions were solved with Comsol Multiphysics finite-element code. The results in terms of coagulation transverse diameters and temperature distributions at the end of the application showed significant differences, especially between Pennes and the modified LTNE and LTE models. The new modified porous media-based models covered the ranges found in the few in vivo experimental studies in the literature and they were closer to the published results with similar in vivo protocol. The outcomes highlight the importance of considering the three models in the future in order to improve thermal ablation protocols and devices and adapt the model to different organs and patient profiles.

The impact of microbubble-enhanced therapeutic ultrasound combined with prothrombin on microwave ablation in the rabbit liver.

AIM: This study aimed to investigate the effect of microbubble-enhanced ultrasound (MEUS) combined with prothrombin on regional hepatic circulation and microwave ablation (MWA) in rabbit livers. MATERIALS AND METHODS: High-pressureamplitude therapeutic ultrasound (TUS) was used to treat 52 surgically exposed livers of healthy New Zealand rabbits: 13 livers were treated with MEUS alone, 13 with MEUS and prothrombin (PMEUS), 13 with ultrasound plus normal saline and 13 with ultrasound plus prothrombin as controls. Contrast-enhanced ultrasound (CEUS) imaging was performed on the exposed livers before and after treatment, and acoustic quantification was done to assess liver perfusion. Then, the liver was divided into two parts, one was used for pathologic examination and the other was ablated with microwave (MWA) and then processedfor pathologic examination. RESULTS: The CEUS images and Peak value after treatment in the PMEUS group were significantly reduced as compared to the remaining 3 groups (p<0.05). Occasional piecemeal hemorrhage was evidenced in the pathological examination in the MEUS group. Obvious cellular degeneration and necrosis with thrombosis were observed in the PMEUS group. Electron microscopy showed endothelial damage in both the MEUS group and PMEUS group. After MWA, coagulated volumes (V) in the PMEUS group were larger than in the remaining 3 groups (p<0.05). The cell ultrastructure disorder wasmore severe in the PMEUS group than in remaining 3 groups. CONCLUSION: PMEUS promotes endothelial injury and produces more obvious thrombotic occlusion, improving the therapeutic effect of MWA on the rabbit liver.

SIRT of liver metastases: physiological and pathophysiological considerations.

Available literature on the differences in circulation and microcirculation of normal liver and liver metastases as well as in rheology of the different radiolabelled microspheres [(99m)Tc-labelled macroaggregates of albumin (MAA), (90)Y-TheraSpheres and (90)Y-SIR-spheres] used in selective internal radiation therapy (SIRT) are reviewed and implications thereof on the practice of SIRT discussed. As a result of axial accumulation and skimming, large microspheres are preferentially deposited in regions of high flow, whereas smaller microspheres are preferentially diverted to regions of low flow. As flow to normal liver tissue is considerably variable between segments and also within one segment, microspheres will be delivered heterogeneously within the microvasculature of normal liver tissue. This non-uniformity in microsphere distribution in normal liver tissue has a significant "liver-sparing" effect on the dose distribution of (90)Y-labelled microspheres. Arterial flow to liver metastases is most pronounced in the hypervascular rim of metastases, followed by the smaller metastases and finally by the central hypoperfused region of the larger metastases. Because of the wide variability in size of labelled MAAs and because of the skimming effect, existing differences in flow between metastatic lesions of variable size are likely exaggerated on (99m)Tc-MAA scintigraphy when compared to (90)Y-TheraSpheres and (90)Y-SIR-spheres (smaller variability in size and probably also in specific activity). Ideally, labelled MAAs would contain a size range similar to that of (90)Y-SIR-spheres or (90)Y-TheraSpheres. Furthermore, the optimal number of MAA particles to inject for the pretreatment planning scintigraphy warrants further exploration as it was shown that concentrated suspensions of microspheres produce more optimal tumour to normal liver distribution ratios. Finally, available data suggest that the flow-based heterogeneous distribution of microspheres to metastatic lesions of variable size might be optimized, that is rendered more homogeneous, through the combined use of angiotensin II and degradable starch microspheres.

Vascular effects of microbubble-enhanced, pulsed, focused ultrasound on liver blood perfusion.

The purpose of this study was to investigate the vascular effects of microbubble-enhanced pulsed high-pressure ultrasound on liver blood perfusion. In the presence of circulating lipid-shell microbubbles, a focused ultrasound transducer was used to transcutaneously treat eight livers of healthy rabbits for perfusion analysis and to treat three livers with the abdomen open for histologic analysis. Twenty-two livers treated with the ultrasound only (n = 11) or microbubbles only (n = 11) served as the controls. The focused ultrasound was operated at a frequency of 1.22 MHz with a peak negative pressure of 4.6 MPa. The liver blood perfusion was estimated by performing contrast-enhanced ultrasound and gray-scale quantification on the livers before and after treatment. A temporary, nonenhanced region occurred in all of the experimental livers. The regional contrast gray-scale values of the experimental group dropped significantly from 88.4 before treatment to 2.7 after treatment. The liver perfusion also demonstrated a gradual recovery over a 60-min period. The liver perfusion of the control groups remained the same after treatment. We found microvascular rupture, hemorrhage and swelling hepatocytes upon histologic examination of the experimental group. Regional liver blood perfusion can be temporarily blocked by microbubble-enhanced focused ultrasound with high-pressure amplitude. These vascular effects can be explained as acute microvascular injury of the liver and may have clinical implications.

Embolization of hepatic arterial branches to simplify hepatic blood flow before yttrium 90 radioembolization: a useful technique in the presence of challenging anatomy.

PURPOSE: In the presence of variant hepatic arterial anatomy, obtaining whole-liver coverage with yttrium 90 (Y90) radioembolization may be challenging. The purpose of this study was to determine whether a technique whereby variant hepatic arterial branches are embolized and then Y90 is administered selectively into one remaining hepatic arterial branch results in whole-liver coverage and effective therapy. A retrospective comparison of treatment response was made between a group of patients who underwent this technique before Y90 administration and a group of patients who received standard Y90 administration as a single dose into the proper hepatic artery or in divided doses into the immediate hepatic artery branches. The rest of the workup and treatment were identical in both groups, including routine embolization of potential nonhepatic, nontarget vessels (e.g., the gastroduodenal artery). METHODS: A total of 32 patients (mean age 56.9 years, range 39-77 years) treated with Y90 between June 2004 and March 2008 were analyzed. The primary malignancy was colorectal in 29, breast in 2, and cholangiocarcinoma in 1. Group 1 comprised 20 patients who had no alterations to their hepatic arterial supply. Group 2 comprised 12 cases who had undergone prior embolization of hepatic arterial branches before administration of Y90. The response to treatment was assessed by comparing standardized uptake value (SUV) on the pre- and postprocedure fludeoxyglucose positron emission tomographic studies of representative lesions within the right and left lobes of the liver. RESULTS: In group 1, significant response (P < 0.001) was seen among right lobe lesions but not among left lobe lesions (P = 0.549). In group 2, there was a significant response among both right (P = 0.028) and left (P = 0.014) lobe lesions. No difference was found in the response of right lobe lesions (P = 0.726) between groups 1 and 2; a significantly greater response was found in group 2 compared to group 1 (P = 0.004) for left lobe lesions. CONCLUSION: Selective Y90 radioembolization after manipulation of hepatic arterial blood supply leads to an even distribution within the entire liver. When variations in hepatic arterial anatomy exist, this technique allows effective whole-liver radioembolization therapy from a single selective arterial injection.

Radioembolization for the treatment of unresectable liver cancer: initial experience at a single center.

PURPOSE: Radioembolization with yttrium-90 microsphere (Y-90) therapy with SIR-Spheres (Sirtex Medical, Lane Cove, Australia) was approved by the Turkish Ministry of Health in April 2008. In this study, we present the preliminary experience at a tertiary care center with early follow-up results of Y-90 therapy, as well as a review of the related literature. MATERIALS AND METHODS: Complete evaluation for radioembolization was performed in 10 patients (8 males, 2 females; mean age, 52.3 years) during an 8-month period at a single center, of which 9 were actually treated with SIR-Spheres(R). All patients underwent meticulous pre- and post-procedural imaging studies to document the therapy response. RESULTS; In order to isolate the target hepatic arterial circulation, following branches were embolized as they were considered as potential gastrointestinal shunts: the gastroduodenal artery (n = 5), right gastric artery (n = 1), and supraduodenal artery (n = 1). Radioembolization therapy could not be performed only in one patient because of a hepatogastric shunt of unknown origin. No significant hepatopulmonary shunting was identified (maximum, 9% shunting). The body surface area method was used to calculate the Y-90 dose in all patients (mean dose, 1.24 GBq). All patients had at least partial response of the targeted liver lesions, according to RECIST (Response Evaluation Criteria in Solid Tumors). CONCLUSION: In comparison to chemoembolization, radioembolization has less systemic toxicity and can be performed as an outpatient procedure, which makes it more attractive to both patients and physicians. From our limited experience, the radioembolization procedure is a promising first-line treatment in unresectable liver cancer; randomized controlled multi-center studies, however, are needed.

Ultrasound monitoring of a novel microwave ablation (MWA) device in porcine liver: lessons learned and phenomena observed on ablative effects near major intrahepatic vessels.

BACKGROUND: Microwave ablation (MWA) is postulated to have several advantages over other thermoablative modalities in the treatment of hepatic tumors. Herein, we use an in vivo porcine model to determine the effect of hepatic blood flow on a novel MWA applicator. METHODS: Four 100-kg pigs underwent hepatic MWA (2,450 MHz, 100 W, 4 min) using a 5.7-mm diameter applicator (Microsulis Americas, Sulis V) inserted near large intrahepatic blood vessels. Real-time monitoring was performed using 3, 5, and 12 MHz diagnostic ultrasound transducers. The ablated zones were sectioned for gross and histological processing. RESULTS: Ablation zones were uniform in shape and size (3-4 cm) and related to power deliver only. Gross and microscopic examination revealed direct extension of ablation zones to the margin of major hepatic blood vessels and occasionally beyond the intended target. Of note, a momentary acoustic white-out occurred around the probe at 25 +/- -1 s in every ablation. DISCUSSION: The Sulis V MWA applicator produced uniform zones of ablation that remain unaffected by convective heat loss. The applicator induced a reproducible but temporary event as seen by ultrasound. Further study is warranted to define the physics, benefits, limits, and clinical safety of this new MWA technology.

Effectivity of laser-induced thermotherapy: in vivo comparison of arterial microembolization and complete hepatic inflow occlusion.

BACKGROUND AND OBJECTIVES: Laser-induced thermotherapy (LITT) is a promising method for local treatment of liver metastases. The aim of this study was to compare the effect of LITT on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. STUDY DESIGN/MATERIALS AND METHODS: In a porcine liver model, LITT (30 W 15 minutes) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle's maneuver, n = 12). LITT lesions were macro- and microscopically assessed after liver dissection. RESULTS: Hepatic inflow occlusion led to a fourfold increase in lesion volume after arterial microembolization and a ninefold increase after complete interruption (6.3. cm3 vs. 27.1 cm3 vs. 58.8 cm3, P < 0.01). CONCLUSIONS: Interrupting hepatic perfusion significantly increases lesion volumes in LITT. This beneficial effect can also be achieved in the percutaneous application mode by LITT combined with arterial microembolization via a hepatic artery catheter.

Kinetic thermal response and damage in laser coagulation of tissue.

BACKGROUND AND OBJECTIVES: Laser induced interstitial coagulation has become a method of treating different types of tumors. Theoretical modeling and analysis may be used to better understand the complex process involved in the laser coagulation and optimized the dosimetry of laser thermotherapy. STUDY DESIGN/MATERIALS AND METHODS: A full dynamic theoretical model was developed to simulate the dynamic evolution of coagulation in tissue, which accounted for the dynamics of the temperature and damage dependence of optical properties, thermal properties, and blood-perfusion rate. The simulation of the temperature distribution, coagulation depth and its hysteresis during laser thermotherapy for full-dynamic model are compared with the calculations from other models. RESULTS: Increased scattering in the near surface of applicator prevents light penetration into deeper region. Moreover, rise in temperature increases both blood flow at the periphery of coagulation region and thermal properties, which reduces the damage depth and its hysteresis. It results in a considerable overestimation of the temperature distribution and damage depth ignoring the dynamic of optical properties. The coagulation would be limited in a smaller region and there is no hysteresis if blood perfusion is regarded as a constant. In contrast, the hysteresis is overestimated if blood perfusion is ignored. Ignoring the dynamics of thermal parameters, there is also overestimation of the rise in temperature and damage depth. CONCLUSIONS: Mathematical modeling techniques that simulate laser coagulation may not provide reliable information unless they take into account these dynamic parameters.

[Veno-occlusive liver disease after total infradiaphragmatic lymphoid irradiation. A rare complication]. / Die Venenverschlusskrankheit der Leber nach infradiaphragmaler total lymphatischer Bestrahlung. Eine seltene Nebenwirkung.

BACKGROUND: Radiotherapy is potentially curative in early stages of follicle center lymphoma. Frequent side effects are pancytopenia, nausea and abdominal discomfort. A radiation-induced liver injury with serious clinical symptoms and changes in liver function is a rare complication. CASE REPORT: Whole abdomen was irradiated in a 49-year-old patient with a centrocytic-centroblastic lymphoma, stage IA (localization: left inguinal region). A total dose of 30 Gy was delivered in a weekly fractionation of five times 1.5 Gy. Kidneys were protected by shielding after a dose of 13.5 Gy, liver blocks were positioned after 25 Gy. During the last 2 days of therapy the patient presented with weight gain, ascites, dyspnoea and elevated liver enzymes. Diagnostics revealed hepatosplenomegaly, ascites and an increased portosystemic pressure gradient. Liver biopsy specimen showed a veno-occlusive disease. Complete relief of symptomatology was achieved within 7 days following placement of a transjugular intrahepatic portosystemic stent-shunt (TIPSS), heparinization and diuretics. Liver enzymes are in the normal range. CONCLUSION: Veno-occlusive disease of the liver (VOD) is a very rare side effect of primary abdominal irradiation of follicle center lymphoma. This complication should be taken into consideration if a patient presents with upper right quadrant pain, ascites and elevation of liver enzymes especially within 4 months following radiotherapy. Genesis of veno-occlusive disease, diagnostics, therapy and a review of the literature are presented.

Acute radiation-induced hepatic injury: evaluation by triphasic contrast enhanced helical CT.

We report a case of radiation-induced hepatic injury as a complication of localized abdominal radiotherapy for epidural spread of non-Hodgkin's lymphoma. The liver was evaluated by triphasic contrast enhanced helical CT scan. Hepatic biopsy demonstrated changes typical of veno-occlusive disease. The pattern of hepatic enhancement resulting from the radiation-induced veno-occlusive process is discussed.

[The cardiovascular system at long periods after radiotherapy of lymphogranulomatosis]. / Serdechno-sosudistaia sistema v otdalennye sroki posle luchevoi terapii limfogranulematoza.

The cardiovascular system was analysed in 157 patients with Hodgkin's disease in a prolonged remission after radiation therapy including irradiation of the mediastinum. The revealed myocardial changes were equally often noted in different irradiation volumes of the heart within the range of 31 to 45 Gy. The number of changes was growing with time. Functional disorders of the pulmonary, hepatic and capillary vessels were also revealed.

Irradiation effects upon ischemic regenerating rat liver cells.

Starch particles injected into the arterial and portal systems of the liver of the rat caused a temporary blockage of the liver circulation and consequent hypoxia in the liver cells. In the regenerating liver this resulted in a 30-40% decrease of thymidine incorporation into DNA, when analysed 1.5 hours after injection. Irradiation-induced cell damage, evaluated by thymidine incorporation 1.5 hours after irradiation with a single dose of X-rays, was not ameliorated by the ischemic condition. It is suggested that this depends on an inhibited nucleotide metabolism and DNA synthesis leading to an additive metabolic hypoxic effect of the starch particles on radiation damage. An equal level of thymidine incorporation, however, was found in an ischemic and a non-ischemic group of animals 16 hours after irradiation. In this case the liver cells in the ischemic group had overcome the additional inhibition of DNA synthesis caused by temporary hypoxia.