Catheter-based in vivo imaging of enzyme activity and gene expression: feasibility study in mice

PURPOSE: To construct and evaluate an interventional catheter-based imaging system for intravital monitoring of molecularly sensitive near-infrared fluorescent probes and optical marker genes. MATERIALS AND METHODS: An imaging device that was based on a miniaturized fiberoptic sensor (MIFS) was built in which images created with a 2.7-F fiberoptic catheter were relayed through a dichroic mirror, through a bandpass filter, and on two independent cameras. This system permitted simultaneous recording of white-light and fluorescent images. Spatial resolution, spectral transmissions, and sensitivity were determined in vitro. In vivo testing was performed in nude mice bearing intraperitoneal tumors that express green fluorescent protein and in a mouse model of ovarian carcinoma with enzyme-activatable near-infrared probes sensitive to tumoral protease activity. Signal intensity on images of tumors and that on images of normal tissue were measured and compared with t test. RESULTS: The catheter, which was advanced through an 18-gauge sheath, showed resolution of 7 line pairs per millimeter and detection limit for fluorochrome Cy5.5 of 1-10 pmol. Detection of endogenous green fluorescent protein gene expression was feasible in tumor nodules smaller than 1 mm in diameter (mean tumor signal intensity, 153.26 +/- 26.45 [SD], compared with that of adjacent nontumoral tissue of 36.73 +/- 11.69; P <.008). Similarly, activation of the near-infrared probe by tumoral proteases could be detected in peritoneal tumor seeds of ovarian cancer model with mean tumor signal intensity of 246.33 +/- 7.77 compared with that of adjacent nontumoral tissue of 41.56 +/- 18.64 (P <.001). Mean contrast-to-noise ratio in the near-infrared channel exceeded white-light contrast-to-noise ratio by a factor of 6.7 (P <.02). CONCLUSION: With this system, in vivo MIFS imaging of gene expression, enzyme activity, and potentially other molecular events is feasible, through direct interventional access to several organs and body cavities and potentially through transvascular approaches.     

Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for early detection--study in mice

PURPOSE: To prospectively evaluate the ability of micro-fiberoptic catheters, which simultaneously record white light and near-infrared (NIR) images, to reveal colonic neoplasms after the intravenous administration of activatable "smart" probes that increase in NIR fluorescence subsequent to protease activation. MATERIALS AND METHODS: The institutional animal care committee approved all animal experiments. CT26 tumor cells were orthotopically implanted into the descending colon of C57BL6/J mice (n=10). Thirteen days later, mice intravenously received either 2 nmol of a protease-sensing probe that had cathepsin B as a major activator (n=5) or saline (control animals [n=5]). One day later, animals were noninvasively examined to the point of the splenic flexure by using microcatheter imaging. Excised colons were subsequently evaluated with epifluorescence imaging, histologic examination, and cathepsin B immunohistochemistry. Student t test was used for statistical analysis, with P<.05 considered to indicate a significant difference. RESULTS: Results with fiberoptic imaging demonstrated that all tumors were visible with the protease-activatable probe, even when they were not readily apparent at white light imaging. A target-to-background ratio (TBR) of 8.86 for tumor to adjacent normal mucosa was achieved in the NIR channel after probe administration (P=.001), whereas white light images resulted in a TBR of 1.14 (P>.5) based on luminosity. The tumoral NIR fluorescence intensity was more than 30-fold greater in probe-injected animals than in control animals, indicating that essentially all of the signal recorded in lesions was from activatable probe administration. Results of immunohistochemistry confirmed cathepsin B overexpression in the tumor compared with adjacent mucosa. CONCLUSION: The use of NIR imaging microcatheters combined with protease-activatable smart probes results in a beacon effect that highlights tumors with high TBRs; this technique thus may be a potentially useful adjunct to white light colonoscopy in the future.     

Real-time MR imaging-guided passive catheter tracking with use of gadolinium-filled catheters

PURPOSE: To test the hypothesis that real-time magnetic resonance (MR) imaging-guided passive catheter tracking is feasible with use of dilute gadolinium (Gd)-filled catheters, to determine the optimal Gd concentration required for tracking, and to measure catheter tip tracking accuracy. MATERIALS AND METHODS: The authors tested a real-time, T1-weighted, two-dimensional, spoiled gradient-recalled echo MR imaging sequence suitable for tracking catheters. In a yogurt phantom, the authors placed 5-F catheters filled with 2%-12% Gd solutions. MR imaging was performed with and without use of a projection dephaser that suppressed background signal. The authors measured signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and enhancement ratio to determine the optimal Gd concentration for catheter depiction. Catheter tip tracking accuracy was measured in an acrylic phantom with use of linear regression analysis, with goodness of fit assessed statistically with the F test. RESULTS: Peak catheter SNR, CNR, and enhancement ratios were obtained with 4%-6% Gd concentrations. Tip tracking accuracy was determined to be +/- 0.41 mm (R2 = 0.99; P < .0001). MR imaging reconstructions were displayed up to 3.1 frames/sec. CONCLUSIONS: Accurate MR imaging-guided passive catheter tracking was feasible in real-time with use of dilute Gd-filled catheters. This technique may have application in MR imaging-guided endovascular procedures.     

A vascular stent as an active component for locally enhanced magnetic resonance imaging: initial in vivo imaging results after catheter-guided placement in rabbits

RATIONALE AND OBJECTIVE: A vascular stent constructed as a high frequency resonator improves the local signal-to-noise ratio at magnetic resonance (MR) imaging. After catheter placement and intravascular expansion, the stent can be used as an inductively coupled coil for MRI. The imaging properties of this balloon-expandable active MRI stent (AMRIS) were evaluated after x-ray fluoroscopy guided placement in the abdominal aorta of five rabbits using MR angiography (MRA) and flow measurements. METHODS: The AMRIS was implanted in the abdominal aorta of five rabbits using a balloon catheter inserted through the common carotid artery. The rabbits were examined by MRA (3D fast low-angle shot) at 1.5 tesla before and after intravenous injection of an iron-oxide-based blood pool contrast medium (dose 50 micro mol Fe/kg) and flow measurements (ECG-triggered phase contrast cine gradient-echo sequence). Signal-to-noise ratios (SNR) were calculated and flow volume curves were generated. The in-stent increase in temperature was measured in vitro using a fiberoptic thermometry system. RESULTS: The SNR was 5.0 +/- 0.6 outside the stent and 23.2 +/- 14.1 within the stent ( < 0.0 5) in plain MRA, 19.5 +/- 5.0 outside and 30.7 +/- 8.2 within the stent ( < 0.05) in contrast enhanced MRA, and 5.8 +/- 1.6 and 13.9 +/- 5.9, respectively ( < 0.05) in the magnitude images of the flow measurements. Flow volume curves within and distal to the stent were comparable. CONCLUSIONS: The expandable active MRI stent produces local signal enhancement in MRA and MR flow measurements after catheter placement and thus may improve assessment of the stented vessel segment by MR imaging.     

Transarterial Delivery of a Biodegradable Single-Agent Theranostic Nanoprobe for Liver Tumor Imaging and Combinatorial Phototherapy

PurposeTo assess selective accumulation of biodegradable nanoparticles within hepatic tumors after transarterial delivery for in vivo localization and combinatorial phototherapy.Materials and MethodsA VX2 hepatic tumor model was used in New Zealand white rabbits. Transarterial delivery of silicon naphthalocyanine biodegradable nanoparticles was performed using a microcatheter via the proper hepatic artery. Tumors were exposed via laparotomy, and nanoparticles were observed by near-infrared (NIR) fluorescence imaging. For phototherapy, a handheld NIR laser (785 nm) at 0.6 W/cm² was used to expose tumor or background liver, and tissue temperatures were assessed with a fiberoptic temperature probe. Intratumoral reactive oxygen species formation was assessed using a fluorophore (2′,7′-dichlorodihydrofluorescein diacetate).ResultsNanoparticles selectively accumulated within viable tumor by NIR fluorescence. Necrotic portions of tumor did not accumulate nanoparticles, consistent with a vascular distribution. NIR-dependent heat generation was observed with nanoparticle-containing tumors, but not in background liver. No heat was generated in the absence of NIR laser light. Reactive oxygen species were formed in nanoparticle-containing tumors exposed to NIR laser light, but not in background liver treated with NIR laser or in tumors in the absence of NIR light.ConclusionsBiodegradable nanoparticle delivery to liver tumors from a transarterial approach enabled selective in vivo tumor imaging and combinatorial phototherapy.     

Active device tracking and high-resolution intravascular MRI using a novel catheter-based, opposed-solenoid phased array coil.

A novel two-element, catheter-based phased array coil was designed and built for both active MR device tracking and high-resolution vessel wall imaging. The device consists of two independent solenoid coils that are wound in opposite directions, connected to separate receive channels, and mounted collinearly on an angiographic catheter. The elements were used independently or together for tracking or imaging applications, respectively. The array's dual functionality was tested on a clinical 1.5 T MRI scanner in vitro, in vivo, and in situ. During real-time catheter tracking, each element gave rise to a high-amplitude peak in the respective projection data, which enabled reliable and robust device tracking as well as automated slice positioning. In vivo microimaging with 240 microm in-plane resolution was achieved in 9 s using the device and TrueFISP imaging. Therefore, a single device was successfully implemented that met the combined requirements of intravascular device tracking and imaging.     

Arm placement of the Cook titanium Petite Vital-Port: results of radiologic placement in 125 patients with cancer.

OBJECTIVE: Patients with cancer require reliable venous access for therapy and phlebotomy. Traditionally, insertion of venous ports has been performed in the operating room. However, the interventional radiology service has recently become involved in the placement of a variety of venous access devices. This study examines the technique and complications associated with the placement of venous ports in the arm for patients with cancer. METHODS: Cook titanium Petite Vital-Ports (Cook Canada, Stouffville, Ont.) were implanted in patients with cancer, and implantation was performed in the medical imaging vascular/interventional suite. Patients were followed prospectively by periodic chart review for a maximum of 42 months after port insertion. Minimum follow-up in patients who did not die from cancer was 6 months. RESULTS: The authors implanted 125 Vital-Ports. The mean duration of port implantation was 265 days (range 2 to 1278 days, total catheter days 33 221). Venous thrombosis developed in 5 patients (4%, or 0.06 episodes/1000 catheter days). Four patients (3.2%, or 0.12 episodes/1000 catheter days) had suspected infection of the port or catheter, and 2 had culture-positive infection (1.6%, or 0.06 episodes/1000 catheter days). Two patients (1.6%, or 0.06 episodes/1000 catheter days) required port or catheter revision owing to mechanical difficulties. CONCLUSION: The Cook titanium Petite Vital-Port, implanted in the arm in the medical imaging vascular/interventional suite, is relatively safe and effective. As a result, it has been widely accepted by the patients and clinicians at the hospital where this study was conducted.     

Real time in vivo non-invasive optical imaging using near-infrared fluorescent quantum dots

RATIONALE AND OBJECTIVE: Deep-tissue optical imaging is of particular interest, as the equipment costs are lower than for competing technologies such as MRI. For this purpose, the development of novel contrast agents with near-infrared (NIR) fluorescence is especially important. We report on the use of NIR semiconductor nanocrystals in deep-tissue in vivo optical imaging. MATERIALS AND METHODS: Semiconductor nanocrystals of CdMnTe/Hg were grown in aqueous solution and then coated with bovine serum albumin (BSA). The nanocrystals were approximately 5 nm in diameter and have a broad fluorescence peak in the NIR (770 nm). Nanocrystals were injected either subcutaneously or intravenously into athymic NCR NU/NU and C3H/HENCR MTV mice and then excited with a spatially broad 633 nm source; the resulting fluorescence was captured with a sensitive CCD camera. RESULTS: We have demonstrated that the nanocrystals are a useful angiographic contrast agent for vessels surrounding and penetrating a murine squamous cell carcinoma in a C3H mouse. Preliminary assessment of the depth of penetration for excitation and emission was done by imaging a beating mouse heart, both through an intact thorax and after a thoracotomy. The temporal resolution associated with imaging the nanocrystals in circulation has been addressed, and the blood clearance for this contrast agent has also been measured. CONCLUSIONS: There was no significant photobleaching or degradation of the nanocrystals after an hour of continuous excitation. The stability of the nanocrystals together with the time resolution of the optical detection makes them particularly attractive candidates for pharmacokinetic imaging studies.     

Perfusion-modulated MR imaging-guided radiofrequency ablation of the kidney in a porcine model.

OBJECTIVE: This study was performed to test the hypothesis that temporary renal ischemia will result in increased thermal lesion size during radiofrequency thermal ablation in the kidney. MATERIALS AND METHODS: Twelve kidneys were treated in six pigs that were placed under general anesthesia in the MR suite, using a 0.2-T open C-shaped MR imaging system. A 4-cm-long, 14-mm-diameter balloon catheter was placed into the aorta using a transfemoral approach, and the balloon was positioned proximal to the renal arteries via guidance with MR imaging. A 2-cm exposed-tip MR-compatible 17-gauge radiofrequency electrode was placed into one kidney under MR fluoroscopy using fast imaging with steady-state free precession (FISP) sequences. Thermal ablation was performed with the electrode tip temperature maintained at 90 +/- 2 degrees C for 10 min. This procedure was repeated in the contralateral kidney. The balloon was inflated during one ablation. Postablation images were obtained, the pigs were sacrificed, and both kidneys of each animal were harvested for pathologic correlation. RESULTS: Technical success was achieved in all animals. The lesion measured 14.2 +/- 2.2 mm (mean +/- standard deviation) for the ischemic kidney versus 8.0 +/- 2.6 mm in the normally perfused kidney (p = 0.00002). No significant complications were noted. In all images, thermal lesions displayed low signal intensity with a sharp rim of high signal intensity best visualized using short tau inversion recovery (STIR) sequences with a mean accuracy of 1.3 +/- 1.2 mm when compared with pathologic findings and a mean contrast-to-noise ratio of 4.9 +/- 2.5. CONCLUSION: We accept the hypothesis that temporary renal ischemia leads to a significantly increased radiofrequency ablation lesion size. We conclude that catheter-based balloon perfusion reduction is feasible, that the procedure does not lead to major complications, and that it can be performed using MR imaging as the sole imaging modality.     

Minimally invasive catheter implantation for regional chemotherapy of the liver: A new percutaneous transsubclavian approach

Purpose Development of a percutaneously implantable catheter system for regional chemotherapy of liver metastases and its application in patients with surgically implanted but dislocated catheters. Methods Thirty-three patients with liver metastases of colorectal tumors were submitted to percutaneous puncture of the subclavian artery and insertion of a catheter whose tip was placed in the proper hepatic artery and whose end was subcutaneously connected with an infusion pump. Results The mean duration of therapy via the percutaneously inserted catheter was 27 weeks (±14 weeks). The most frequent complication was disconnection of the therapy catheter from the tube of the infusion pump. Eighty percent of all complications were corrected by reintervention. The therapy drop-out rate due to catheter-associated complications was 9%. Conclusion Percutaneous insertion of a catheter for regional chemotherapy of the liver is a relatively uncomplicated method with high patient acceptance and simple access for reintervention.     

Tomographic fluorescence imaging of tumor vascular volume in mice

PURPOSE: To prospectively determine the feasibility of imaging vascular volume fraction (VVF) and its therapeutic inhibition in mouse models of cancer with three-dimensional fluorescence molecular tomography (FMT). MATERIALS AND METHODS: All studies were approved by the institutional animal review committee and were in accordance with National Institutes of Health guidelines. CT26 colon tumor-bearing mice were imaged with FMT after intravenous administration of long-circulating near-infrared fluorescent blood-pool agents optimized for two nonoverlapping excitation wavelengths (680 and 750 nm). A total of 58 mice were used for imaging VVF to evaluate the following: (a) differences in ectopically and orthotopically implanted tumors (n = 10), (b) cohorts of mice (n = 24) treated with anti-vascular endothelial growth factor (VEGF) antibody, (c) serial imaging in same animal to determine natural course of angiogenesis (n = 4), and (d) dose response to anti-VEGF therapy (n = 20). To compare groups receiving antiangiogenic chemotherapy, analysis of variance was used. RESULTS: Fluorochrome concentrations derived from FMT measurements were reconstructed with an accuracy of +/-10% at 680 nm and +/-7% at 750 nm and in a depth-independent manner, unlike at reflectance imaging. FMT measurements of vascular fluorescent probes were linear, with concentration over several orders of magnitude (r > 0.98). VVFs of colonic tumors, which varied considerably among animals (3.5% +/- 1.5 [standard deviation]), could be depicted with in vivo imaging in three dimensions with less than 5 minutes of imaging and less than 3 minutes of analysis. The natural course of angiogenesis and its inhibition could be reliably imaged and depicted serially in different experimental setups. CONCLUSION: FMT is a tomographic optical imaging technique that, in conjunction with appropriate fluorescent probes, allows quantitative visualization of biologic processes.     

Diagnosis of arthritis using near-infrared fluorochrome Cy5.5

PURPOSE: Near-infrared range fluorescence (NIRF) imaging is a potential tool to diagnose biologic processes in vivo. This applicability study sought to define whether imaging with fluorochrome Cy5.5 can identify arthritis in murine antigen-induced arthritis (AIA). MATERIALS AND METHODS: On day 7 of AIA (n = 9 mice), fluorescence intensities in inflamed and contralateral knee joints (the latter as internal control) were measured before and after intravenous injection of Cy5.5 (until 72 hours). Cy5.5 joint deposition was verified by confocal laser-scanning microscopy. Dye phagocytosis was evaluated in cultured macrophages (cell line PMJ2-R) by FACS analysis. Cy5.5 binding to serum protein was tested by NIRF scanning and gel electrophoresis. RESULTS: Between 2 and 72 hours, the arthritic knee joints showed significantly higher fluorescence intensities compared with contralateral joints. Microscopy confirmed Cy5.5 deposition in the synovial membrane. Cultured macrophages actively phagocytosed Cy5.5. Cy5.5 bound mainly to albumin as the main serum protein. CONCLUSION: NIRF imaging with Cy5.5 can identify arthritic joints in vivo, likely due to nonspecific deposition.     

Calibration with currently available low-radiopacity catheters for scaling in digital quantitative coronary angiography.

RATIONALE AND OBJECTIVES: In quantitative coronary angiography, the absolute diameters of coronary artery lumina are obtained by using a catheter as a scaling device. METHODS: We examined the effect of x-ray opacity on the accuracy of calibration methods that use such catheters by varying the concentration of contrast medium in the catheters in phantom experiments with a digital cine imaging system. RESULTS: With contrast-filled, currently available catheters, the average increase in the measured calibration factor from the gold standard (as determined by using a measuring scale) was 1.0% and 0.4% in the 13-cm and 17-cm image-intensifier modes, respectively, compared with -9.9% and -12.4% for catheters without contrast medium. The corresponding figures for catheters of the previous generation that lacked contrast medium were 1.0% and 0.4%, respectively. The image contrast of previous-generation catheters filled with saline was closer to that of current-generation catheters filled with contrast medium than that of current-generation catheters filled with saline. CONCLUSIONS: When used for quantitative coronary angiography by digital angiography, currently available low-radiopacity catheters give more accurate data when filled with contrast medium.     

In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

Purpose The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Methods Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. Results The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Conclusion Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity.     

Transendocardial delivery of extracellular myocardial markers by using combination X-ray/MR fluoroscopic guidance: feasibility study in dogs

PURPOSE: To demonstrate the feasibility of using a combination of x-ray fluoroscopic and magnetic resonance (MR) fluoroscopic (ie, x-ray/MR fluoroscopy) guidance for left ventricular (LV) catheterization and transendocardial delivery of extracellular tissue markers. MATERIALS AND METHODS: Experiments were performed in six dogs by using an x-ray/MR fluoroscopy system. The arterial guide wire and catheter were advanced into the heart with x-ray fluoroscopic guidance. The dogs were injected with 0.5, 1.0, and 2.0 mL of iohexol. For passive catheter tracking, a steady-state free precession MR imaging sequence was used. A steerable dual-lumen catheter was used to transendocardially inject a mixture of gadodiamide (0.05 mol/L) plus Evans blue dye (3%). An electrocardiographically gated dual-inversion-recovery MR imaging sequence was used to visualize the myocardial delivery of the gadodiamide-blue dye mixture. A high concentration of gadodiamide (0.5 mol/L) was used to demarcate the borders of the area of interest, or "hit the target." Blood pressure, heart rate, and oxygen saturation were measured before and after the intervention. Analysis of variance, Scheffé, and paired Student t tests were used for data analysis. RESULTS: LV catheterization via arterial access was feasible with two-dimensional x-ray fluoroscopic and three-dimensional MR fluoroscopic guidance. Delivery of the gadodiamide-blue dye mixture and the consequences of the procedure were monitored with MR imaging. Gadolinium-enhanced regions were bright on T1-weighted MR images, but they varied in size as a function of injectant volume. The mean sizes of these regions were 1.5% +/- 0.6 of the LV after the 0.5-mL injection of the mixture and 7.0% +/- 0.5 of the LV after the 2.0-mL injection (P <.001, Scheffé test). The corresponding mean sizes of the blue dye-enhanced regions were 2.3% +/- 0.6 and 8.3% +/- 0.4, respectively (P <.001). A high concentration of gadodiamide caused signal intensity loss around the gadolinium-enhanced regions. CONCLUSION: Transendocardial delivery of potential therapeutic solutions is feasible with x-ray/MR fluoroscopic guidance. The injection catheter can be navigated with MR imaging guidance to hit the target.     

MRI—3D ultrasound—X-ray image fusion with electromagnetic tracking for transendocardial therapeutic injections: In-vitro validation and in-vivo feasibility

Myocardial infarction (MI) is one of the leading causes of death in the world. Small animal studies have shown that stem-cell therapy offers dramatic functional improvement post-MI. An endomyocardial catheter injection approach to therapeutic agent delivery has been proposed to improve efficacy through increased cell retention. Accurate targeting is critical for reaching areas of greatest therapeutic potential while avoiding a life-threatening myocardial perforation. Multimodal image fusion has been proposed as a way to improve these procedures by augmenting traditional intra-operative imaging modalities with high resolution pre-procedural images. Previous approaches have suffered from a lack of real-time tissue imaging and dependence on X-ray imaging to track devices, leading to increased ionizing radiation dose. In this paper, we present a new image fusion system for catheter-based targeted delivery of therapeutic agents. The system registers real-time 3D echocardiography, magnetic resonance, X-ray, and electromagnetic sensor tracking within a single flexible framework. All system calibrations and registrations were validated and found to have target registration errors less than 5 mm in the worst case. Injection accuracy was validated in a motion enabled cardiac injection phantom, where targeting accuracy ranged from 0.57 to 3.81 mm. Clinical feasibility was demonstrated with in-vivo swine experiments, where injections were successfully made into targeted regions of the heart.     

Catheter tracking and visualization using 19F nuclear magnetic resonance.

This work presents an investigation into catheter visualization and localization using 19F nuclear magnetic resonance (NMR) in conjunction with proton imaging. For this purpose, the imaging capabilities of a standard system were extended to allow for 19F excitation and signal detection. Two modes of operation were implemented: 1) a real-time tracking mode that provides tip tracking and automatic slice position updates interleaved with real-time, interactive proton imaging; and 2) a non-real-time catheter length visualization mode in which the entire length of a catheter can be assessed. Initial phantom experiments were conducted with the use of an angiographic balloon catheter filled with the blood substitute perfluorooctylbromide (PFOB). Using limited bandwidth excitation centered at the resonances of the CF2 groups of PFOB, we found that sufficient signal could be received to facilitate tip tracking during catheter motion and length visualization for various catheter configurations. The present approach is considered a promising alternative to existing methods, which either are associated with safety concerns (if active markers are employed) or suffer from insufficient, direction-dependent contrast (if passive visualization is used). Furthermore, our approach enables visualization of the entire length of the catheter. The proposed method provides a safe technique that, unlike electrical or optical devices, does not require modification of commercially available catheters.     

Radiologic placement of side-hole catheter with tip fixation for hepatic arterial infusion chemotherapy

PURPOSE: To investigate the technical outcome of radiologic catheter placement with use of a side-hole catheter with distal fixation for hepatic arterial infusion chemotherapy. MATERIALS AND METHODS: Between January 1993 and September 1999, 426 patients were referred to our department to undergo intraarterial infusion chemotherapy for unresectable malignant liver tumors. A subclavian artery was exposed under local anesthesia and a catheter was inserted. After inserting the tip of the side-hole catheter into the gastroduodenal artery, splenic artery, or peripheral branch of the hepatic artery, the catheter tip was fixed to the vessel with use of coils and a mixture of n-butyl cyanoacrylate (NBCA) and iodized oil. The proximal end of the catheter was connected to an implanted port, and the port system was embedded subcutaneously. RESULTS: Placement was successful in 425 of 426 patients (99.8%) in a mean time of 76 minutes. Catheter dislodgement was noted in 12 patients (2.8%). Cumulative patency rates of the hepatic artery calculated according to the Kaplan-Meier method for the entire group were 91.0%, 81.4%, and 58.1% at 6 months and 1 and 2 years, respectively. Complications related to catheter placement were observed in nine cases and included dysfunction of the implanted system (n = 3), significant bleeding around the implanted port (n = 2), improper infusion of NBCA and iodized oil (n = 2), and cerebral infarction (n = 2). CONCLUSION: Radiologic catheter placement via a subclavian artery with side-hole catheter placement with distal fixation for hepatic arterial infusion chemotherapy is a highly successful procedure with a reduced risk of catheter dislodgment and arterial occlusion.     

Assessment of unspecific near-infrared dyes in laser-induced fluorescence imaging of experimental arthritis

OBJECTIVE: The aim of the study is to evaluate in vivo fluorescence imaging of experimental inflammatory joint disease by applying two different near-infrared (NIR) dyes in a model of Borrelia-induced Lyme arthritis. MATERIALS AND METHODS: Forty mice, 20 with Lyme arthritis and 20 controls, were examined. Two nonspecific NIR carbocyanine dyes, indocyanine green (ICG) and a hydrophilic carbocyanine derivative (1,1'-bis-[4-sulfobutyl] indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium salt [SIDAG]), were administered intravenously at two doses. Fluorescence images were acquired before and during 120 seconds after injection of cyanine dyes. For both dyes, the area under the curve (AUC) was determined for the interval between 40 and 80 seconds after injection. In addition, the slope of the signal decrease was compared among animal groups. Results were compared with histological findings. RESULTS: The general temporal fluorescence intensity course for ICG was characterized by a rapid increase, with a peak at 40-50 seconds followed by a decrease; conversely for SIDAG, by a slow increase. AUC analysis for both dyes showed that the fluorescence signal differed significantly between controls and arthritic animals (P < .05). Within these groups, there were significant differences between the two doses investigated. ICG differed significantly between control and arthritic animals in the slope of the signal decrease for both doses investigated (P < .05). Histological examination showed early stages of inflammation in arthritic animals. CONCLUSIONS: NIR fluorescence imaging based on the pharmacokinetic behavior of ICG or SIDAG is a promising approach to detect inflammatory joint changes of experimental arthritis. Moreover, SIDAG is suited to differentiate inflammatory and noninflammatory joints 24 hours after dye application.     

16层螺旋CT结肠三维成像与仿真内镜的临床应用研究

目的 探讨16层螺旋CT三维成像与仿真内镜在结肠肿瘤诊断中的应用价值。资料与方法 应用Lightspeed 16CT对26例纤维结肠镜活检证实的结肠癌(19例)和结肠息肉(7例)进行容积扫描．在AW4-2工作站进行三维成像和仿真内镜观察．并与纤维结肠镜结果相比较。结果 25例三维成像效果良好．仿真内镜与纤维结肠镜显示基本一致,1例因肠道准备不彻底,成像效果欠佳,但不影响诊断;CT仿真结肠镜(CTVC)结合2D多平面重建(MPR)和透明显示(Raysum)图像,可以提供更多信息,有助于病变的准确定位、定性。结论16层螺旋CT仿真内镜结合三维成像能达到与纤维结肠镜同样的敏感性和特异性,加上MPR、RavSun图像技术可以提供比纤维结肠镜更丰富的信息。