Jonathan B. Kruskal

PERCUTANEOUS RADIOFREQUENCY TISSUE ABLATION : OPTIMIZATION OF PULSED-RADIOFREQUENCY TECHNIQUE TO INCREASE COAGULATION NECROSIS

PURPOSE To develop a computerized algorithm for pulsed, high-current percutaneous radiofrequency (RF) ablation, which maximally increases the extent of induced coagulation necrosis. MATERIALS AND METHODS An automated, programmable algorithm for pulsed-RF deposition was designed to permit high-current deposition by periodically reducing current for 5-30 seconds during RF application. Two strategies for pulsed-RF deposition were evaluated: (i) constant peak current (900-1,800 mA) of variable duration and (ii) variable peak current (1,200-2,000 mA) for a specified minimum duration. The extent of induced coagulation was compared to results obtained with continuous (lower current) RF application. Trials were performed in ex vivo calf liver (n = 115) and in vivo porcine liver (n = 30) and muscle (n = 18) with use of 2-4-cm tip, internally cooled electrodes. RESULTS For 3-cm electrodes in ex vivo liver, applying pulsed-RF with constant peak current for 12 minutes produced 3.5 cm +/- 0.2 of necrosis. Greater necrosis was produced with use of the variable current strategy, in which 4.5 cm +/- 0.2 of coagulation was achieved with use of an initial current > or =1,500 mA (minimum peak-RF duration of 10 sec, with 15 sec of reduced current to 100 mA between peaks; P < .01). This variable peak current algorithm also produced 3.7 cm +/- 0.6 of necrosis in in vivo liver, and 6.5 cm +/- 0.9 in in vivo muscle. Without pulsing, a maximum of 750 mA, 1,100 mA, and 1,500 mA could be applied in ex vivo liver, in vivo liver, and in vivo muscle, respectively, which resulted in 2.9 cm +/- 0.2, 2.4 cm +/- 0.2, and 5.1 cm +/- 0.4 of coagulation (P < .05, all comparisons). CONCLUSIONS A variable peak current algorithm for pulsed-RF deposition can increase coagulation necrosis diameter over other ablation strategies. This innovation may ultimately enable the percutaneous treatment of larger tumors.

Fibrin and Fibrinogen-Related Antigens in Patients with Stable and Unstable Coronary Artery Disease

Coronary-artery thrombosis may be important in the pathogenesis of unstable angina at rest. To study this possibility, we measured the serum concentrations of fibrin-related antigen, D dimer (the principal breakdown fragment of fibrin), and fibrin monomer (an intermediate product of fibrin formation) in the serum of five groups of subjects. These included 10 healthy controls, 10 controls with noncardiac pain, and three groups of 10 patients each with chronic stable angina, unstable angina at rest, or acute myocardial infarction. The concentration of fibrin-related antigen (normal range, 48 to 184 ng per milliliter) was normal in the control patients with noncardiac pain (63 to 202 ng per milliliter) and in patients with chronic stable angina (95 to 186), but it was increased in patients with unstable angina (401 to 2507) or acute myocardial infarction (470 to 1930) (P less than 0.001). D dimer concentrations in patients with unstable angina (178.3 to 310.6 ng per milliliter) or acute myocardial infarction (103.9 to 321.6) were higher than those in patients with chronic stable angina (28.6 to 52.1), in controls with noncardiac pain (44.7 to 53.1), and in healthy controls (40.4 to 50.3) (P less than 0.001). Concentrations of fibrin monomer were highest in patients with acute myocardial infarction (247.5 to 571.3 ng per milliliter) (P less than 0.001), intermediate in those with unstable angina (54.7 to 241.7) (P less than 0.001), and normal (normal range, 14.5 to 19.8 ng per milliliter) in controls with noncardiac pain (12.0 to 18.4). and patients with chronic stable angina (10.7 to 17.6). These findings suggest the presence of an active thrombotic process in patients with unstable angina at rest or acute myocardial infarction. The data do not prove that the coronary arteries were the site of the thrombotic process, but the observations are consistent with the hypothesis that thrombus formation may have an important role in the pathogenesis of these conditions.

Hepatic microcirculatory changes after reperfusion in fatty and normal liver transplantation in the rat

The hepatic microcirculation in fatty and normal liver grafts in ACI rats was investigated using in vivo microscopy. Six groups were studied. They were: normal and fatty control livers (sham operated), 6-hr cold University of Wisconsin solution (UW)-preserved fatty and normal liver grafts (survival conditions, fatty and normal liver grafts), 18-hr cold UW-preserved fatty livers (nonsurvival conditions, fatty liver graft), and 24-hr cold UW-preserved normal livers (nonsurvival conditions, normal liver grafts). Fatty livers in all groups were found to have narrow and irregular sinusoids with blood cell adhesions to endothelial cells. The number of adhesions increased as the preservation time increased. Sinusoidal blood flow area decreased as the preservation time increased and was correlated with survival in both normal and fatty liver grafts. The phagocytic activity of Kupffer cells (corrected for flow) increased as the preservation time increased. The phagocytic Kupffer cell activity of the 18-hr preserved fatty liver group was greater than the activity of any other group. These features may cause liver cell death and contribute to primary graft nonfunction after transplantation of a fatty liver.

Impact of CT-guided drainage in the treatment of diverticular abscesses : Size matters

OBJECTIVE Our objective was to determine whether abscess size can be used as a discriminating factor to guide management of patients with diverticular abscesses. MATERIALS AND METHODS We performed a word search of our CT database between July 2001 and July 2002 for the CT diagnosis of diverticulitis. CTs were retrospectively reviewed as consensus opinion of two reviewers. CTs were evaluated for presence of an abscess, its location, maximum diameter, and feasibility of percutaneous abscess drainage. Abscesses were categorized into smaller than 3 cm and larger than or equal to 3 cm, and the management of these groups was compared. RESULTS Thirty-one abscesses were noted in 30 (17%) of 181 patients with a CT diagnosis of diverticulitis. Twenty-two (73%) of 30 patients had 23 abscesses, all of which were smaller than 3 cm and were treated and resolved with antibiotics alone (p < 0.001). Eight (36%) of 22 required surgical treatment. Eight (26%) of 31 abscesses had a maximum diameter larger than or equal to 3 cm. Four (50%) of eight patients with abscesses 3.4-4.1 cm were treated with antibiotics alone. Four (50%) of eight abscesses, all larger than 4.1 cm, were treated with CT-guided drainage and one abscess required repeat drainage. After resolution of symptoms, surgery was performed in five (62.5%) of eight of the larger abscesses. CONCLUSION Patients with abscesses smaller than 3 cm in size can be treated with antibiotics alone and, in some cases, as outpatients, and may not uniformly require surgery. This is also likely true for patients with abscesses 3-4 cm in size, although our results in this group were limited by a small sample size. Patients with abscesses larger than or equal to 4 cm can be managed with CT-guided abscess drainage followed by referral for surgical treatment.

Role of virtual computed tomographic colonography in patients with colorectal cancers and obstructing colorectal lesions

PURPOSE: The aim of this study was to assess the ability of computed tomographic colonography to diagnose colorectal masses, stage colorectal cancers, image the proximal colon in obstructing colorectal lesions, and evaluate the anastomoses in patients with previous colorectal surgery. METHODS: We prospectively performed computed tomographic colonography examinations in 34 patients (20 males; mean age, 64.2; range, 19–91 years): 20 patients had colorectal masses (defined at endoscopy as intraluminal masses 2 cm or larger), 7 patients had benign obstructing colorectal strictures, and 7 patients had a prior colorectal resection. Final tumor staging was available in all 16 patients who had colorectal cancers and 15 patients were referred after incomplete colonoscopy. The ability of computed tomographic colonography to stage colorectal cancers, identify synchronous lesions in patients with colorectal masses, and image the proximal colon in patients with obstructing colorectal lesions was assessed. RESULTS: Computed tomographic colonography identified all colorectal masses, but overcalled two masses in patients who were either poorly distended or poorly prepared. Computed tomographic colonography correctly staged 13 of 16 colorectal cancers (81 percent) and detected 16 of 17 (93 percent) synchronous polyps. Computed tomographic colonography overstaged two Dukes Stage A cancers and understaged one Dukes Stage C cancer. A total of 97 percent (87/90) of all colonic segments were adequately visualized at computed tomographic colonography in patients with obstructing colorectal lesions compared with 60 percent (26/42) of segments at barium enema (P<0.01). Colonic anastomoses were visualized in all nine patients, but in one patient, computed tomographic colonography could not distinguish between local tumor recurrence and surgical changes. CONCLUSION: Computed tomographic colonography can accurately identify all colorectal masses but may overcall stool as masses in poorly distended or poorly prepared colons. Computed tomographic colonography has an overall staging accuracy of 81 percent for colorectal cancer and is superior to barium enema in visualizing colonic segments proximal to obstructing colorectal lesions.

Improved Coagulation with Saline Solution Pretreatment during Radiofrequency Tumor Ablation in a Canine Model

PURPOSE To determine whether pretreatment with local NaCl injection can increase radiofrequency (RF)-induced coagulation in a large animal model. MATERIAL AND METHODS Multiple canine venereal sarcomas (n = 25) were implanted subcutaneously in eight mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to a diameter of 4.2-6.3 cm (5.1 cm +/- 0.7). Internally cooled RF ablation (1-cm tip; 12 min; pulsed technique; 2,000-mA maximum) was performed. Tumors were pretreated with 6 mL of 18%, 24%, or 36% NaCl injected intratumorally under direct ultrasound guidance after RF electrode insertion, and this treatment was compared to RF treatment without NaCl injection and to 36% NaCl injection without RF ablation. Impedance measurements and remote thermometry were performed. These measurements and resultant coagulation were compared. RESULTS Significantly greater RF heating (73 degrees C +/- 11 degrees C at 20 mm) was observed when the tumors were treated with 24% or 36% NaCl pretreatment, compared to the 47 degrees C +/- 5 degrees C observed when 18% or no NaCl was injected (P <.02). In the 36% NaCl group, the entire tumor (5.2 cm +/- 0.8 diameter) was completely ablated in every case, with coagulation extending several centimeters into the surrounding tissues. By comparison, control tumors (without NaCl injection) contained coagulation measuring 3.1 cm +/- 0.2, surrounded by viable, well-perfused tumor (P <.01), and 36% NaCl alone produced 2.7 cm +/- 0.6 of patchy necrosis. CONCLUSIONS Pretreatment with intratumoral injection of small volumes of highly concentrated NaCl markedly increases RF heating and coagulation in a large animal tumor model. The complete destruction of tumors 5 cm in diameter or larger suggests that this substantial increase may be achieved for tumor ablation in clinical practice.

Peer Review in Diagnostic Radiology: Current State and a Vision for the Future

Over the past decade, the level of interest in improving the quality of healthcare in the United States has increased. New requirements established by regulatory organizations require the ongoing practice-based evaluation of physician performance. Peer review, a key process in physician performance evaluation, is geared primarily toward measuring diagnostic accuracy. Accuracy may be measured in terms of interpretive agreement or disagreement during a blinded double reading or in workstation-integrated evaluations. Each method of assessing diagnostic accuracy has strengths and weaknesses that should be carefully considered before it is implemented in a particular departmental or institutional setting.

Beneficial effects of CD39/ecto-nucleoside triphosphate diphosphohydrolase-1 in murine intestinal ischemia-reperfusion injury.

CD39 (ecto-nucleoside triphosphate diphosphohydrolase-1; E-NTPDase-1), is highly expressed on quiescent vascular endothelial cells and efficiently hydrolyzes extracellular ATP and ADP to AMP and ultimately adenosine. This action blocks extracellular nucleotide-dependent platelet aggregation and abrogates endothelial cell activation. However, CD39 enzymatic activity is rapidly lost following exposure to oxidant stress. Modulation of extracellular nucleotide levels may therefore play an important role in the pathogenesis of vascular injury. Acute ischemic injury of the bowel is a serious medical condition characterized by high mortality rates with limited therapeutic options. Here we evaluate the effects of cd39-deletion in mutant mice and the use of supplemental NTPDase or adenosine in influencing the outcomes of intestinal ischemia-reperfusion. Wild-type, cd39-null, or hemizygous cd39-deficient mice were subjected to intestinal ischemia. In selected animals, 0.2 U/g apyrase (soluble NTPDase) was administered prior to re-establishment of blood-flow. In parallel experiments adenosine/amrinone was infused over 60 min during reperfusion periods. Survival rates were determined, serum and tissue samples were taken. Intravital videomicroscopy and studies of vascular permeability were used to study platelet-endothelial cell interactions and determine capillary leakage. In wild-type animals, ischemia reperfusion injury resulted in 60% mortality within 48 hours. In mutant mice null or deficient for cd39, ischemia reperfusion-related death occurred in 80% of animals. Apyrase supplementation protected all wild-type animals from death due to intestinal ischemia but did not fully protect cd39-null and cd39-hemizygote mice. Adenosine/amrinone treatment failed to improve survival figures. In wild type mice, platelet adherence to postcapillary venules was significantly decreased and vascular integrity was well preserved following apyrase administration. In cd39-null mice, ischemia-reperfusion induced marked albumin leakage indicative of heightened vascular permaeability when compared to wild-type animals (p=0.04). Treatment with NTPDase or adenosine supplementation abrogated the increased vascular permeability in ischemic jejunal specimens of both wild-type mice and cd39-null. CD39 activity modulates platelet activation and vascular leak during intestinal ischemia reperfusion injury in vivo. The potential of NTPDases to maintain vascular integrity suggests potential pharmacological benefit of these agents in mesenteric ischemic injury.

Perfusion MDCT Enables Early Detection of Therapeutic Response to Antiangiogenic Therapy

OBJECTIVE The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. MATERIALS AND METHODS Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. RESULTS All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p < 0.05). Although perfusion in the control tumors changed little from day 0 to day 14 (day 0, 18.1 +/- 9.2 mL/min/100 g; day 4, 15.8 +/- 5.6; day 9, 21.7 +/- 12.2; day 14, 27.7 +/- 34), in the sorafenib group, the mean blood flow was significantly lower at day 4 (5.2 +/- 3.2 mL/min/100 g, 77% decrease), day 9 (6.4 +/- 4.0 mL/min/100 g, 66% decrease), and day 14 (6.3 +/- 5.2 mL/min/100 g, 83% decrease) compared with day 0 (23.8 +/- 11.6 mL/min/100 g) (p < 0.05). Poor correlation was seen between changes in blood flow and tumor volume for days 0-9 (r(2) = 0.34), 4-9 (r(2) = 0.0004), and 9-14 (r(2) = 0.16). However, when comparing day 4 images with days 9 and 14 images, seven of 14 (50%) sorafenib-treated tumors had focal areas of new perfusion that correlated with areas of histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). CONCLUSION Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

Dynamic Intrahepatic Flow and Cellular Alterations during Radiofrequency Ablation of Liver Tissue in Mice

PURPOSE The purpose of this study was to identify microvascular and other associated changes that occur in the liver during focal heating with monopolar radiofrequency (RF). MATERIALS AND METHODS Intravital video microscopy was performed on exteriorized transilluminated livers of 15 live mice during RF-induced heating of liver parenchyma. Microvascular flow parameters, flow reversibility, microbubble formation, phagocytic activity, and endothelial permeability were recorded throughout a range of tip temperatures (40 degrees C-95 degrees C). RESULTS During RF application, five discrete zones extended outward from the electrode surface: (i) tissue coagulation, (ii) cellular edema/necrosis, (iii) sinusoidal stasis, (iv) parenchymal shunting, and (v) normal liver tissue. Reversal of stasis in sinusoids and small (<25 microm) vessels occurred at tip temperatures below 50 degrees C. This zone of stasis corresponded to the hyperemic zone on histologic analysis. Although alterations in permeability and phagocytic activity were first identified at 43 degrees C, tip temperatures higher than 55 degrees C always produced local endothelial leakiness to carbon microparticles at the periphery and always inhibited phagocytic activity. At tip temperatures higher than 95 degrees C, microbubble formation occurred with bubbles ultimately tracking through necrotic tissue into patent sinusoids. Larger peripheral vessels (>30 microm) limited extension of coagulation. CONCLUSION Although coagulation occurs at tip temperatures higher than 50 degrees C, RF heating induced reversible microvascular stasis at temperatures lower than 50 degrees C. Increased sinusoidal endothelial permeability occurs at near-coagulative temperatures. Therefore, targeted endovascular microparticle delivery through this leaky endothelium may provide an additional and complimentary adjunct for RF ablation therapy.