Fiducial markers for MR histological correlation in ex vivo or short-term in vivo animal experiments: a screening study

PURPOSE: To test injectable fiducial markers for magnetic resonance (MR) histological correlation in ex vivo or in vivo animal experiments. MATERIALS AND METHODS: A total of 35 potential markers were tested ex vivo in pork muscle. The end-points were: 1) visibility, size, and shape on MR images and at macroscopic examination; 2) 24-hour stability; and 3) microscopic appearance. Selected markers were injected in vivo (rabbit's muscle and breast tumor tissue) to test their three-hour in vivo stability and their potential toxicity. Finally, different dilutions of the two best markers were assessed again through the same screening tests to determine whether their size on MR images could be customized by dilution. RESULTS: Two fluid acrylic paints containing inorganic pigments were found to be potentially interesting markers. On MR images, they created well-defined susceptibility artifacts. The markers made with iridescent bronze paint (iron oxide coated mica particles) were readily visible on microscopy and their size on MR images could be customized by dilution. The iridescent stainless steel paint (iron, chromium, nickel) created ex vivo the smallest markers in tissue but needed colloidal iron staining to be visible on microscopy and could not be easily diluted. CONCLUSION: Fluid acrylic paints are potentially interesting markers for MR histological correlation. Further studies are needed to assess their long-term properties.     

Resistance to hoop stress in balloon expandable stents: evaluation in an ex vivo model

RATIONALE AND OBJECTIVES: To develop a new model for a more realistic evaluation of radial strength and elastic recoil of balloon expandable stents using a new ex vivo model in human cadaver bifurcations of the aorta. MATERIALS AND METHODS: Four different stents (each group n = 10) were implanted in cadaver common iliac arteries. Randomization was performed either to right or left iliac artery. The specimens were cast filled with silicone caoutchouc and after 24 hours the vascular walls including the stents were removed from the hardened casts. The weight of the cast cylinders of the stents was measured in air and in purified water: the difference of the two values resulted in the buoyancy force and because of that the volume of the bodies as a relative degree for the radial strength could be calculated. The findings were correlated with the workbench tests of the manufacturers. RESULTS: Manufacturer's workbench tests were incomparable because of wide spread specifications. There was a significant difference between the theoretical maximal volume (0.866 mL) and the real cast volumes ( P< 0.025) that corresponds directly to the elastic recoil of the stents. The following mean real cast volumes were measured (corrected for 1 cm): Sinus-Stent 0.677 mL, Palmaz-Stent 0.708 mL, Jostent 0.715 mL, Saxx-Stent 0.732 mL, thus reflecting the various degree of radial strength; therefore, the ranking in radial strength resistance was Saxx, Jostent, Palmaz, and Sinus. CONCLUSION: High radial strength and low elastic recoil are important requirements of any stent design. Ex vivo tests unlike in vitro physical testing facilitate a realistic evaluation of the inherent stent characteristics. The model used in this study proved to be uniformly valid for physical stent design testing.     

Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR cholangiography: results of an in vivo phase-I clinical evaluation

The purpose of this study was to investigate the time course of contrast enhancement in bile ducts and the gallbladder (GB) after injection of gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA). In a clinical phase-I study, MR imaging at 1.5T was performed in 16 healthy volunteers with four different doses of Gd-EOB-DTPA (10, 25, 50, and 100 μmol/kg b. w., four volunteers per dosage). The study protocol comprised a heavily T1-weighted fast multiplanar gradient-echo (GE) sequence before and at increasing intervals for up to 360 min after injection of Gd-EOB-DTPA. The signal enhancement was evaluated in extra- and intrahepatic bile ducts as well as in the GB. In all 16 volunteers the common bile duct showed intense signal enhancement beginning 5–16 min after injection (mean 10 min) and persisting for at least 120 min in 4 subjects and for 360 min in 12 subjects. The duration of signal enhancement was significantly (p < 0.05) longer for higher doses (50, 100 μmol/kg) than for lower doses (10, 25 μmol/kg). Intrahepatic bile ducts were hyperintense as compared with liver parenchyma in all subjects receiving 10 μmol/kg from approximately 50–120 min after contrast agent application. Intrahepatic bile ducts were not displayed using the higher doses, probably because of the strong enhancement of the liver parenchyma. Gallbladder contrasting was achieved in all cases beginning 7–33 min after injection (mean 19 min) and remained visible for up to 360 min in 94 %. Hyperintense visualization of normal extrahepatic bile ducts as well as the GB is regularly achieved with the hepatobiliary contrast agent Gd-EOB-DTPA. The dosage for hyperintense visualization of intrahepatic bile ducts is 10 μmol/kg. Received 6 December 1995; Revision received 21 March 1996; Accepted 25 March 1996     

An ex vivo biomechanical evaluation of a hydroxyapatite cement for use with kyphoplasty.

BACKGROUND AND PURPOSE: Previous ex vivo biomechanical studies have shown that kyphoplasty with polymethylmethacrylate cement increases vertebral body (VB) strength and restores VB stiffness and height after compression fracture. The purpose of the current study was to determine if a hydroxyapatite cement used as a void filler during kyphoplasty provides mechanical stabilization similar to that of a polymethylmethacrylate cement. METHODS: Simulated compression fractures were experimentally created in 33 osteoporotic VBs harvested from female cadaver spines. VBs were assigned to one of three groups: 1) kyphoplasty with a custom mixture of Simplex P; 2) kyphoplasty with BoneSource; and 3) no treatment. The kyphoplasty treatment consisted of inserting a balloon-like device into the VB via both pedicles, inflating the tamp, and filling the created void with Simplex P bone cement or BoneSource. VBs in the no-treatment group received no interventions. Pre- and posttreatment heights were measured, and the repaired VBs were recompressed to determine posttreatment strength and stiffness values. RESULTS: Kyphoplasty with altered Simplex P restored strength, whereas kyphoplasty with BoneSource and the no-treatment protocol both resulted in significantly weaker VBs relative to initial strength. All treatments resulted in significantly less stiff VBs relative to their initial condition. All VBs lost significant height after initial compression, but a significant amount of lost height was restored by kyphoplasty with either cement. CONCLUSION: Kyphoplasty with either cement significantly restored VB height. Kyphoplasty with altered Simplex P resulted in stronger repairs than did no treatment or kyphoplasty with BoneSource.     

Osteoid osteoma in an ex vivo animal model: temperature changes in surrounding soft tissue during CT-guided radiofrequency ablation

PURPOSE: To assess temperature changes in the soft tissue surrounding bone during radiofrequency (RF) ablation of osteoid osteoma in an ex vivo animal model. MATERIALS AND METHODS: Intracortical cavities were created in fresh bovine long bone specimens obtained from a slaughterhouse as models for osteoid osteoma. Three groups of three specimens each were defined according to the thickness (1, 3, and 5 mm) of the cortical bone lamella separating the nidus from the periosteum. Three thermocouples were applied to the soft tissue surrounding the bone in defined distances (0, 5, and 10 mm) from the periosteum. Before RF ablation, the thickness of the cortical bone lamella was documented at computed tomography. Specimens were heated in a 37 degrees C basin. As soon as the measured temperature in the cavity of the specimen reached 35 degrees C, RF ablation was performed for 400 seconds, with a target temperature of 95 degrees C. During RF ablation, continuous measurements were performed simultaneously with digital thermometers. No simulation of vessel perfusion was used. The effect of the thickness of residual osseous lamella and the effect of the distance between the thermocouple and the periosteum were tested with an analysis of variance. Post hoc Bonferroni tests were performed. RESULTS: Mean maximum temperatures of 69.1 degrees, 51.3 degrees, and 42.5 degrees C for 1-mm lamella; 59.2 degrees, 46.5 degrees, and 41.1 degrees C for 3-mm lamella; and 50.6 degrees, 44.8 degrees, and 40.0 degrees C for 5-mm lamella were measured 0, 5, and 10 mm, respectively, from the periosteum. Significant temperature differences were shown with analysis of variance and post hoc tests for the three groups of bone lamella thickness and distance (P < .001). CONCLUSION: In the model of osteoid osteoma, the surrounding temperature (soft tissue) during RF ablation was shown to depend on the thickness of the cortical bone lamella and the distance from the periosteum.     

MR histological correlation: a method for cutting specimens along the imaging plane in animal or ex vivo experiments

PURPOSE: To assess a method aimed at cutting histological specimens along the magnetic resonance (MR) imaging plane. MATERIAL AND METHODS: The method is performed in two steps: the imaging plane (defined by three acrylic paint markers) is made horizontal under MR guidance by using a mobile platform that can be rotated in three directions (PlaneFinder device [PFD]); then, the specimen is embedded in wax and cut horizontally. Three-dimensional images parallel to the markers' plane were obtained on 31 pork muscles containing a central hole with a pyramidal shape, with a technique of reference (RT images) and with PFD (PF images), before and after fixation. The last 17 fixed specimens were cut in the markers' plane (tissue section [TS] images). The central hole area (CHA) in the markers' plane was used to compare RT, PF, and TS images. Using a workstation, PF images were rotated and translated to estimate the shift along each direction that could explain the entire CHA difference between RT, PF, and TS images (maximum error, worst-case scenario). RESULTS: Excellent correlation was found between RT and PF images (r = 0.989, slope = 1.0175), PF and TS images (r = 0.991, slope = 1.0058), and RT images on fresh specimens and TS images (r = 0.979, slope = 1.0732). For each step, the maximum angle error was < or = 3 degrees in 88-95% of the specimens. CONCLUSION: Our methodology can be used to cut specimens along the imaging plane with high accuracy.     

MR colonography: development of optimized method with ex vivo and in vivo systems

An ex vivo magnetic resonance (MR) colonographic system with a bovine colon with polyps of predetermined dimensions was developed for evaluation and optimization of different combinations of imaging sequences and intraluminal contrast agents. Findings were then applied during in vivo testing in human subjects. The results show that optimized contrast and lesion conspicuity and minimized motion artifacts can be obtained with true fast imaging with steady-state precession combined with water as an intraluminal contrast agent.     

In vivo and in vitro evaluation of Gd-DTPA-polylysine as a macromolecular contrast agent for magnetic resonance imaging.

Polylysine covalently linked to moieties of gadopentetate (Gd-DTPA), for use as a macromolecular blood pool marker for contrast material-enhanced magnetic resonance imaging (MRI), was characterized by means of physicochemical measurements and pharmacokinetics in rats and rabbits and compared with Gd-DTPA. Gd-DTPA-polylysine was composed of a series of polymers of different molecular sizes that on average were labeled with 60 to 70 Gd-DTPA moieties (average molecular weight, 48,700 daltons [D]). For the macromolecular compound Gd-DTPA-polylysine, relaxivity was three times higher than that of Gd-DTPA. The LD50 value of 17 mmol/kg reflects a fairly high acute intravenous tolerance of the macromolecular compound in mice. Even though the volume of distribution of Gd-DTPA-polylysine in rabbits approached the extracellular fluid space (indicating that the macromolecular compound was also leaking slowly into the interstitial space), the half-life of distribution of the macromolecular compound in the extracellular fluid space was significantly prolonged, thus making the compound suitable as a blood pool marker for MRI. In rats the elimination of Gd-DTPA-polylysine occurred predominantly via the renal route. High-pressure liquid chromatography-size-exclusion chromatography of the fractionated urine samples revealed that the renal clearance must be the integral sum of the separate clearances of each molecular weight species. No biodegradation of the polypeptide was observed, and biodistribution studies revealed only minimal retention of Gd in the body of the rat.     

Single-step radiosynthesis and in vivo evaluation of a novel fluorine-18 labeled hippurate for use as a PET renal agent

ObjectiveThe objective of this study was to investigate a new fluorine-18 labeled hippurate, m-cyano-p-[¹⁸ F]fluorohippurate ([¹⁸ F]CNPFH), as a potential radiopharmaceutical for evaluating renal function by PET.Methods[¹⁸ F]CNPFH was synthesized by a direct one-step nucleophilic aromatic substitution using an ¹⁸ F-for-[N(CH₃)₃]⁺-reaction. In vivo stability was determined by HPLC analysis of urine collected from a healthy rat at 30 min p.i. of [¹⁸ F]CNPFH. The plasma protein binding (PPB) and erythrocyte uptake of [¹⁸ F]CNPFH were determined using blood collected from healthy rats at 5 min p.i. Biodistribution studies were conducted in healthy rats at 10 min and 1 h p.i. of [¹⁸ F]CNPFH. Dynamic PET/CT imaging data were acquired in normal rats. For comparison, the same rats underwent an identical imaging study using the previously reported p-[¹⁸ F]fluorohippurate ([¹⁸ F]PFH) renal agent.Results[¹⁸ F]CNPFH demonstrated high in vivo stability with no metabolic degradation. The in vivo PPB and erythrocyte uptake of [¹⁸ F]CNPFH were found to be comparable to those of [¹⁸ F]PFH. Biodistribution and dynamic PET/CT imaging studies revealed a rapid clearance of [¹⁸ F]CNPFH primarily through the renal–urinary pathway. However, unlike [¹⁸ F]PFH, a minor (about 12%) fraction was eliminated via the hepatobiliary route. The PET-derived [¹⁸ F]CNPFH renograms revealed an average time-to-peak (T_max) of 3.2 ± 0.4 min which was similar to [¹⁸ F]PFH, but the average time-to-half-maximal activity (11.4 ± 2.8 min) was found to be higher than that of [¹⁸ F]PFH (7.1 ± 1.3 min).ConclusionsOur in vivo results indicate that [¹⁸ F]CNPFH has renogram characteristics similar to those of [¹⁸ F]PFH, however, the unexpected hepatobiliary elimination is adding undesirable background signal in the PET images.     

99Tcm-tetrofosmin:一种评价体内P-糖蛋白功能变化的显像剂

99Tcm-tetrofosmin是一种制备简便、使用广泛的显像剂,在体内和体外它均为多药耐药蛋白和P-糖蛋白转运的底物.它的特点与99Tcm-甲氧基异丁基异腈(99Fcm-MIBI)相似但不完全一样.现有的文献提示,有关多药耐药性功能显像和体内多药耐药性功能调节的临床研究可以通过99Tcmtetrofosmin和99cm-MIBI显像来进行,但是两者似乎不能互换.     

99Tcm-tetrofosmin:一种评价体内P-糖蛋白功能变化的显像剂

99Tcm-tetrofosmin是一种制备简便、使用广泛的显像剂,在体内和体外它均为多药耐药蛋白和P-糖蛋白转运的底物.它的特点与99Tcm-甲氧基异丁基异腈(99Fcm-MIBI)相似但不完全一样.现有的文献提示,有关多药耐药性功能显像和体内多药耐药性功能调节的临床研究可以通过99Tcmtetrofosmin和99cm-MIBI显像来进行,但是两者似乎不能互换.     

超极化水作为MRI对比剂:大鼠模型活体成像的可行性

目的评价一种MRI灌注技术的可行性,采用动态原子核极化(DNP)技术对大鼠连续地给予超极化水来提供影像对比。材料与方法研究方案经过本单位动物保护和使用委员会批准,并进行随访监督。12只雄性Wistar大鼠麻醉后,分别将注射管放置于皮下(n=3)、腹膜内(n=3)、主动脉(n=3)和颈动脉(n=3)。采用自制系统在1.5TMRI的0.35T边缘磁场将水质子以DNP方法超极化后,将其不断地输入大鼠体内。采集快速梯度回波和损毁梯度MRI序列。计算并比较影像的信噪比。结果在所有的注射部位,影像的信噪比都明显改善,流动对比效应明显。在皮下和腹腔内注射时,大约注射5s后就可观察到水的灌注轨迹。在主动脉内注射时,可观察到4.2cm长的动脉内流动。在右侧颈动脉注射时,可观察到右侧大脑半球的强化效应。采用超极化水后所获得的图像,与没有注射极化水或注射非极化水者相比,信噪比明显提高,颈动脉的信噪比提高13%～27%,而其他部位提高444%～2900%。结论连续地注射超极化水可获得灌注对比MRI影像,从而在活体大鼠模型获得局部的血管造影或脑组织灌注信息。     

Evaluation of 18F-annexin V as a PET imaging agent in an animal model of apoptosis.

Annexin V is a 36-kDa protein that binds with high affinity to phosphatidylserine lipids in the cell membrane. Because one of the earliest measurable events in apoptosis is the eversion of phosphatidylserine from the inner membrane leaflet to the outer cell surface, annexin V has proven useful for detecting the earliest stages of apoptosis. METHODS: Annexin V was radiolabeled with 18F using N-succinimidyl-4-18F-fluorobenzoic acid chemistry, to a specific activity of 555-925 kBq/mug of protein. 18F-Annexin V (14.8-51.8 MBq) was administered intravenously to rats after pretreatment with cycloheximide (5 mg/kg) to induce liver apoptosis, and the injected rats were imaged by PET over 2 h. After imaging, rats were dissected and individual organs were weighed and counted. RESULTS: Pretreatment of rats with cycloheximide resulted in a 3- to 9-fold increase in uptake of 18F-annexin V in the liver of treated animals at 2 h, compared with controls. By morphologic analysis, treated livers showed a 3- to 6-fold higher level of apoptosis than controls, with higher levels also seen with longer exposure to cycloheximide. Terminal deoxynucleotide end-labeling (TUNEL) assays performed on liver slices showed that cycloheximide induced a 5- to 8-fold increase in the number of TUNEL-positive nuclei. These TUNEL results correlated with the uptake of 18F-annexin V in dissected liver tissue, with an r2 value of 0.89. Biodistribution analysis of normal rats showed highest uptake of 18F-annexin V in the kidneys and urinary bladder, indicating rapid renal clearance of 18F-annexin V metabolites. CONCLUSION: The PET data, the organ-specific uptake data from dissection, and the morphologic and TUNEL measures of apoptosis together indicate that 18F-annexin V binds specifically to apoptotic tissues in this model of chemically induced apoptosis in rat liver. The short physical half-life of 18F-annexin V and the rapid clearance of its metabolites to the urinary system suggest that 18F-annexin V will be useful in early assessment of the clinical response to cancer therapy in individual patients.     

应用白芨建立门静脉高压动物模型

目的寻求制作门静脉高压动物模型的最佳方法，并以此为基础从事肝硬化后门静脉血液动力学基础研究。方法以3组共15只兔为动物模型，分别以0.2％、0．4％、0.8％浓度的白芨粉为栓塞材料，开腹注入兔门静脉内，手术前后行门静脉测压、血管造影及病理学检查，最长观察时间阎周.结果以0．4％浓度白芨粉制作门静脉高压模型最佳，4周后肝脏体积缩小20％，门静脉压平均升高40％，病理呈典型坏死后肝硬化表现。结论以白芨粉为栓塞材料制作肝硬化门静脉高压动物模型方法简单、效果可靠已重复性好.以不同浓度的白芨栓塞剂来控制坏死后肝纤维化的程度是本试验的一大特点,本动物模型的建立对深入研究肝硬化门静脉高压的成因及治疗措施有着重要意义。     

MR-guided percutaneous cryotherapy of the liver: in vivo evaluation with histologic correlation in an animal model

The purpose of this study was to evaluate the feasibility of MR-guided percutaneous cryotherapy of the porcine liver and to correlate the resulting tissue necrosis with MR imaging and histology. Using an MR-compatible, argon-based cryotherapy system (CryoHit; Galil Medical Ltd., Israel) with 2- and 3-mm diameter tapered cryotherapy probes, MR-guided percutaneous cryotherapy was performed in seven pigs (mean body weight, 40 kg) under general anesthesia in a short-bore magnet (1.5 T ACS NT; Philips, The Netherlands) using an ultrafast T2-weighted single-shot LoLo TSE sequence and a T1-weighted gradient-echo sequence. The frozen liver tissue was depicted accurately on fast T2- and T1-weighted sequences, providing precise delineation of the ablated tissue volume. On follow-up postcontrast MR controls, the cryolesions appeared avascular. They decreased in size compared with the initially frozen volume down to 70% at a 2-week follow-up. Histologically, a coagulation necrosis with a close correlation to the MR follow-up examinations was objectified. No cryotherapy-related complications occurred. J. Magn. Reson. Imaging 2001;13:50-56.     

Evaluation of nonperfused myocardial ischemia with MRI and an intravascular USPIO contrast agent in an ex vivo pig model

The ultrasmall superparamagnetic iron oxide (USPIO) preparation NC100150 Injection (Clariscan; Nycomed Imaging, Oslo, Norway) was tested for its ability to delineate nonperfused myocardium under steady-state conditions. An experimental animal model of focal myocardial ischemia induced by ligation of the distal part of the left anterior descending artery was used. The contrast agent was administered in four doses: 0, 4, 8, and 12 mg Fe/kg body weight. Magnetic resonance examination ex vivo, including T1-, T2-, and T2*-weighted sequences, was performed. Nonperfused myocardium was determined by fluorescein. The best delineation of nonperfused myocardium was found with a T1-weighted inversion recovery/turbo spin-echo sequence and doses of 4 and 8 mg Fe/kg body weight, where 95% of the volume was discernible at the dose of 4 mg Fe/kg body weight. The results suggest that steady-state imaging by T1-weighted sequence with the use of NC100150 Injection to delineate nonperfused myocardium is feasible. J. Magn. Reson. Imaging 2000;12:866-872.     

Establishment of a large animal model for research on transbronchial arterial intervention for lung cancer

PURPOSEWe aimed to evaluate whether bronchial artery can supply a percutaneously inoculated canine transmissible venereal tumor (CTVT) in a lung tumor model.METHODSFresh CTVT tissue blocks were percutaneously inoculated into unilateral or bilateral lungs of six immunosuppressed dogs at the mid zone of the middle or lower lobe. Tumor growth was monitored by computed tomography (CT). Ten weeks after inoculation, pulmonary arterial digital subtraction angiography (DSA), bronchial arterial DSA, transpulmonary arterial contrast-enhanced multislice CT, transbronchial arterial contrast-enhanced multislice CT (BA-MSCT), and transpulmonary arterial lipiodol multislice CT were performed.RESULTSTumor growth was seen in all 10 inoculated sites, with a maximum diameter of 2.734±0.138 cm at 10th week. Bronchial arterial blood supply was evident in 9 nodules on DSA, and was equivocal in one which was later demonstrated on BA-MSCT. No obvious pulmonary arterial blood supply was observed in any of the nodules. Lipiodol deposition was displayed in two of the small distant metastases, which indicated that pulmonary artery was involved in the supply of the metastases.CONCLUSIONOur results demonstrated bronchial arterial blood supply in this new lung cancer model. This model may be used in further research on transbronchial arterial intervention for lung cancer.

Bronchial arterial infusion chemotherapy (BAI) for lung cancer was introduced into clinical practice 50 years ago (1–3). Theoretically, better reductions in tumor size and symptoms, and less adverse effects of anticancer drugs could be achieved with direct infusion of high-density chemotherapeutics into tumors. However, BAI for lung cancer is not widely accepted. In the last two decades, only a few small case series were published in the English literature showing favorable results (4–9). This may be explained by several reasons: the outcomes have not been confirmed, severe complications have been reported (10, 11), the pharmacokinetics of BAI has not been fully understood, the indications and the treatment protocols have not been defined (4, 12). In the near future, the role of BAI or other transbronchial arterial therapy in the combined treatment of lung cancer may be reappraised, given the poor 5-year survival rate of less than 17% despite improvements in therapeutic management (13).Unfortunately, there is currently no large animal lung cancer model for fundamental research on transbronchial arterial therapy. In 2002, Ahrar et al. (14) developed a canine lung tumor model by intra-arterial or percutaneous inoculation of canine transmissible venereal tumor (CTVT) fragments, which was later used for study on percutaneous radiofrequency ablation (15). It is well known that metastatic lung cancer receives blood supply from both pulmonary artery and bronchial artery, with peripheral tumors having a predominant pulmonary circulation and central tumors having a predominant bronchial circulation (16). Our study goal is to evaluate the blood supply of this large animal lung tumor model.     

Percutaneous radiofrequency ablation of lung tumors in a large animal model

PURPOSE: Percutaneous radiofrequency ablation (RFA) is accepted therapy for liver tumors in the appropriate clinical setting, but its use in lung neoplasms remains investigational. We undertook this study to evaluate the feasibility and immediate effectiveness of RFA for treatment of both solitary pulmonary nodules and clusters of lung tumors in a large animal model. MATERIALS AND METHODS: Percutaneous RFA of 14 lung tumors in five dogs was performed under CT guidance. Animals were euthanatized 8-48 hours after the procedure. The lungs and adjacent structures were harvested for gross and histopathologic evaluation. RESULTS: Five solitary pulmonary nodules (range, 17-26 mm) and three clusters of three nodules each (range, 7-17 mm per nodule) were treated with RFA. All ablations were technically successful. Perilesional ground-glass opacity and small asymptomatic pneumothoraces (n = 4) were visualized during the RFA sessions. One dog developed a large pneumothorax treated with tube thoracostomy but was euthanatized 8 hours post-RFA for persistent pneumothorax and continued breathing difficulty. Follow-up CT 48 hours post-RFA revealed opacification of the whole lung segment. Gross and histopathologic evaluation showed complete thermal coagulation necrosis of all treated lesions without evidence of any viable tumor. The region of thermal coagulation necrosis typically extended to the lung surface. Small regions of pulmonary hemorrhage and congestion often surrounded the areas of coagulation necrosis. CONCLUSIONS: RFA can be used to treat both solitary pulmonary nodules and clusters of tumor nodules in the canine lung tumor model. This model may be useful for development of specific RFA protocols for human lung tumors.