Bariatric Radioembolization: A Pilot Study on Technical Feasibility and Safety in a Porcine Model.

PURPOSE: To evaluate feasibility of left gastric artery (LGA) yttrium-90 ((90)Y) radioembolization as potential treatment for obesity in a porcine model. MATERIALS AND METHODS: This study included 8 young female pigs (12-13 weeks, 21.8-28.1 kg). Six animals received infusions of (90)Y resin microspheres (46.3-105.1 MBq) into the main LGA and the gastric artery arising from the splenic artery. Animal weight and serum ghrelin were measured before treatment and weekly thereafter. Animals were euthanized 69-74 days after treatment, and histologic analyses of mucosal integrity and ghrelin immunoreactive cell density were performed. RESULTS: Superficial mucosal ulcerations < 3.0 cm(2) were noted in 5 of 6 treated animals. Ghrelin immunoreactive cell density was significantly lower in treated versus untreated animals in the stomach fundus (13.5 vs 34.8, P < .05) and stomach body (11.2 vs 19.8, P < .05). Treated animals gained less weight than untreated animals over the study duration (40.2 kg ± 5.4 vs 54.7 kg ± 6.5, P = .053). Average fundic parietal area (165 cm(2) vs 282 cm(2), P = .067) and average stomach weight (297.2 g vs 397.0 g, P = .067) were decreased in treated versus untreated animals. Trichrome staining revealed significantly more fibrosis in treatment animals compared with control animals (13.0 vs 8.6, P < .05). No significant differences were identified in plasma ghrelin concentrations (P = .24). CONCLUSIONS: LGA (90)Y radioembolization is promising as a potential treatment for obesity. A larger preclinical study is needed to evaluate the safety and efficacy of this procedure further.

The impact of an antireflux catheter on target volume particulate distribution in liver-directed embolotherapy: a pilot study.

PURPOSE: To determine if there are differences in hepatic distribution of embolic particles following infusion with a standard end-hole catheter versus an antireflux microcatheter. MATERIALS AND METHODS: This prospective study included nine patients (age, 48-86 y) enrolled for treatment of hepatocellular carcinoma (n = 6), liver-dominant metastatic disease (n = 2), or intrahepatic cholangiocarcinoma (n = 1) with resin yttrium-90 ((90)Y) microspheres. Before (90)Y treatment, each patient received two same-day sequential lobar infusions of technetium 99m ((99m)Tc) macroaggregated albumin (MAA) via a conventional end-hole catheter and an antireflux microcatheter positioned at the same location. Differences in technetium 99m-MAA distribution within tumor and nontarget sites were evaluated by single-photon emission computed tomography (SPECT) on a qualitative and semiquantitative basis. The antireflux microcatheter was used for the ensuing (90)Y treatment, with posttreatment (90)Y positron emission tomography/computed tomography to assess distribution of (90)Y microspheres. RESULTS: Decreases in hepatic nontarget embolization were found in all patients when the antireflux catheter was used. These decreases ranged from a factor of 0.11 to a factor of 0.76 (mean, 0.42; σ = 0.19), representing a 24%-89% reduction. Increased tumor deposition was also noted in all patients, ranging from a factor of 1.33 to a factor of 1.90 (mean, 1.68; σ = 0.20), representing a relative increase of 33%-90%. Both findings were statistically significant (P < .05). CONCLUSIONS: Although this pilot study identified differences in the downstream distribution of embolic particles when the antireflux catheter was used, further investigation is needed to determine if these findings are reproducible in a larger patient cohort and, if so, whether they are associated with any clinical impact.

Improved Accuracy of Minimally Invasive Transpedicular Screw Placement in the Lumbar Spine With 3-Dimensional Stereotactic Image Guidance: A Comparative Meta-Analysis.

STUDY DESIGN: This study compares the accuracy rates of lumbar percutaneous pedicle screw placement (PPSP) using either 2-dimensional (2-D) fluoroscopic guidance or 3-dimensional (3-D) stereotactic navigation in the setting of minimally invasive spine surgery (MISS). This represents the largest single-operator study of its kind and first comprehensive review of 3-D stereotactic navigation in the setting of MISS. OBJECTIVE: To examine differences in accuracy of lumbar pedicle screw placement using 2-D fluoroscopic navigation and 3-D stereotaxis in the setting of MISS. SUMMARY OF BACKGROUND DATA: Surgeons increasingly rely upon advanced image guidance systems to guide minimally invasive PPSP. Three-dimensional stereotactic navigation with intraoperative computed tomography offers well-documented benefit in open surgical approaches. However, the utility of 3-D stereotaxis in the setting of MISS remains incompletely explored by few studies with limited patient numbers. MATERIALS AND METHODS: A total of 599 consecutive patients underwent minimally invasive lumbar PPSP aided by 3-D stereotactic navigation. Postoperative imaging and medical records were analyzed for patient demographics, incidence and degree of pedicle breach, and other surgical complications. A total of 2132 screw were reviewed and compared with a meta-analysis created from published data regarding the placement of 4248 fluoroscopically navigated pedicle screws in the setting of MISS. RESULTS: In the 3-D navigation group, a total of 7 pedicle breaches occurred in 6 patients, corresponding to a per-person breach rate of 1.15% (6/518) and a per-screw breach rate of 0.33% (7/2132). Meta-analysis comprised of data from 10 independent studies showed overall breach risk of 13.1% when 2-D fluoroscopic navigation was utilized in MISS. This translates to a 99% decrease in odds of breach in the 3-D navigation technique versus the traditional 2-D-guided technique, with an odds ratio of 0.01, (95% confidence interval, 0.01-0.03), P<0.001. CONCLUSIONS: Three-dimensional stereotactic navigation based upon intraoperative computed tomography imaging offers markedly improved accuracy of percutaneous lumbar pedicle screw placement when used in the setting of MISS.

Intraprocedural yttrium-90 positron emission tomography/CT for treatment optimization of yttrium-90 radioembolization.

Radioembolization with yttrium-90 ((90)Y) microspheres relies on delivery of appropriate treatment activity to ensure patient safety and optimize treatment efficacy. We report a case in which (90)Y positron emission tomography (PET)/computed tomography (CT) was performed to optimize treatment planning during a same-day, three-part treatment session. This treatment consisted of (i) an initial (90)Y infusion with a dosage determined using an empiric treatment planning model, (ii) quantitative (90)Y PET/CT imaging, and (iii) a secondary infusion with treatment planning based on quantitative imaging data with the goal of delivering a specific total tumor absorbed dose.

Treatment modification of yttrium-90 radioembolization based on quantitative positron emission tomography/CT imaging.

Treatment activity for yttrium-90 ((90)Y) radioembolization when calculated by using the manufacturer-recommended technique is only partially patient-specific and may result in a subtumoricidal dose in some patients. The authors describe the use of quantitative (90)Y positron emission tomography/computed tomography as a tool to provide patient-specific optimization of treatment activity and evaluate this new method in a patient who previously received traditional (90)Y radioembolization. The modified treatment resulted in a 40-Gy increase in absorbed dose to tumor and complete resolution of disease in the treated area within 3 months.

High yield expression of serine/threonine protein phosphatase type 5, and a fluorescent assay suitable for use in the detection of catalytic inhibitors.

Protein phosphatase type 5 (PP5) belongs to the PPP family of serine/threonine protein phosphatases and is expressed in most, if not all, human tissues. Although the physiological roles played by PP5 are not yet clear, PP5 is found in association with several proteins that influence intracellular signaling networks initiated by hormones (i.e., glucocorticoids) or cellular stress (i.e., hypoxia, oxidative stress). Recently, studies conducted with short interfering RNA and antisense oligonucleotides indicate that PP5 plays an important role in the regulation of stress-induced signaling cascades that influence both cell growth and the onset of apoptosis. Therefore, the identification of small molecule inhibitors of PP5 is desired for use in studies to further define the biological/pathological roles of PP5. Such inhibitors may also prove useful for development into novel antitumor agents. Here we describe methods to express and purify large amounts of biologically active PP5c, an inhibitor titration-based assay to determine the amount of PP5 in solution, and a fluorescent phosphatase assay that can be used to screen chemical libraries and natural extracts for the presence of catalytic inhibitors.

Safety and efficacy of combined micropuncture and shallow angle femoral artery access for neurovascular angiography.

INTRODUCTION: The AXERA 2 low-angle vascular access device utilizes a dual arteriotomy mechanism in which the standard access tract is compressed by a vascular sheath inserted over the second, low-angle tract. It is unknown whether this device could be effectively used with 21-gauge micropuncture access, as the micropuncture introducer makes a larger arteriotomy than the 19-gauge needle provided with the AXERA 2 system. MATERIALS AND METHODS: A retrospective review was performed on 189 patients who underwent common femoral artery access for diagnostic cerebrovascular angiography using either combined micropuncture and AXERA 2 access or standard access with manual pressure hemostasis. Demographic and procedural data were reviewed along with complications related to vascular access and times to bed elevation, ambulation and discharge. RESULTS: Combined micropuncture and AXERA 2 access was performed on 110 patients and 79 patients had standard access. The AXERA device was successfully used in 91.8% of the cases. Demographic data, anticoagulant use and sheath sizes were similar between both subsets. Use of the AXERA 2 was associated with two bleeding complications (1.8%) compared with 10 (12.7%) with manual pressure hemostasis alone. Institution-specific protocol allowed shorter mean manual compression time, as well as shorter times to ambulation and discharge with the AXERA 2. CONCLUSIONS: Use of the AXERA 2 device with micropuncture access did not infer increased bleeding risk than standard arterial access in this patient series. The considerable incidence of device use failures suggests a learning curve associated with its use.

A Microdosimetric Analysis of Absorbed Dose to Tumor as a Function of Number of Microspheres per Unit Volume in 90Y Radioembolization.

UNLABELLED: Differences in maximum tolerable absorbed dose to normal liver between (90)Y radioembolization and external-beam radiation therapy have been explained by citing differences in absorbed-dose heterogeneity at the microscopic level. We investigated microscopic absorbed-dose heterogeneity in radioembolization as a function of the number of microspheres per unit volume in tumor. The goal was to determine what effect the number of microspheres may have, if any, on tumor control in (90)Y radioembolization. METHODS: (90)Y PET/CT data were combined with microscopic probability-density functions describing microsphere clustering to provide realistic simulation using Monte Carlo modeling on both a macroscopic and a microscopic level. A complete microdosimetric analysis using 100-µm voxels was performed on the basis of (90)Y PET/CT data from 19 tumors treated using radioembolization. Simulations were performed with average tumor microsphere-number densities from 200 to 70,000 spheres/mL. Monte Carlo simulations of each tumor and number density were repeated 20 times to establish SE. A 2-way balanced ANOVA was used to determine whether differences in microsphere-number density affected common tumor-dose metrics. RESULTS: Decreasing the microsphere-number density resulted in a decrease in D70, the minimum dose to 70% of the tumor. The slope of the dose-volume histogram also decreased with decreasing microsphere-number density in all tumors. Compared with a density of 50,000 spheres/mL, decreases in D70 were statistically significant below 20,000 spheres/mL. However, these differences are unlikely to have clinical significance until the density decreases to below 5,000 spheres/mL. Although D70 was decreased at a low microsphere-number density, one can compensate for decreases by an increase in the average tumor-absorbed dose, that is, by increasing the radioembolization treatment dose. CONCLUSION: Differences in microsphere-number density may have an effect on microscopic tumor absorbed-dose inhomogeneity. These results begin to explain differences in treatment planning strategies between glass and resin radioembolization devices.

How Sensitive Is the Upper Gastrointestinal Tract to 90Y Radioembolization? A Histologic and Dosimetric Analysis in a Porcine Model.

In 90Y radioembolization, nontarget embolization to the stomach or small bowel can result in gastrointestinal injury, a rare but difficult to manage clinical complication. However, dosimetric thresholds for toxicity to these tissues from radioembolization have never been evaluated in a controlled setting. We performed an analysis of the effect of 90Y radioembolization in a porcine model at different absorbed-dose endpoints. METHODS: Six female pigs underwent transfemoral angiography and infusion of 90Y-resin microspheres into arteries supplying part of the gastric wall. Esophagogastroduodenoscopy was performed after 4 wk to assess interim gastrointestinal health. Animals were monitored for side effects for 9 wk after 90Y infusion, after which they were euthanized and their upper gastrointestinal tracts were excised for analysis. Histologic sections were used to map microsphere location, and a microdosimetric evaluation was performed to determine the absorbed-dose profile within the gastrointestinal wall. RESULTS: 90Y radioembolization dosages from 46.3 to 105.1 MBq were infused, resulting in average absorbed doses of between 35.5 and 91.9 Gy to the gastric wall. No animal exhibited any signs of pain or gastrointestinal distress through the duration of the study. Excised tissue showed 1-2 small (<3.0 cm2) healed or healing superficial gastric lesions in 5 of 6 animals. Histologic analysis demonstrated that lesion location was superficial to areas of abnormally high microsphere deposition. An analysis of microsphere deposition patterns within the gastrointestinal wall indicated a high preference for submucosal deposition. Dosimetric evaluation at the luminal mucosa performed on the basis of microscopic microsphere distribution confirmed that 90Y dosimetry techniques conventionally used in hepatic dosimetry provide a first-order estimate of absorbed dose. CONCLUSION: The upper gastrointestinal tract may be less sensitive to 90Y radioembolization than previously thought. Lack of charged-particle equilibrium at the luminal mucosa may contribute to decreased toxicity of 90Y radioembolization compared with external-beam radiation therapy in gastrointestinal tissue. Clinical examples of injury from 90Y nontarget embolization have likely resulted from relatively large 90Y activities being deposited in small tissue volumes, resulting in absorbed doses in excess of 100 Gy.

The evolution of image-guided lumbosacral spine surgery.

Techniques and approaches of spinal fusion have considerably evolved since their first description in the early 1900s. The incorporation of pedicle screw constructs into lumbosacral spine surgery is among the most significant advances in the field, offering immediate stability and decreased rates of pseudarthrosis compared to previously described methods. However, early studies describing pedicle screw fixation and numerous studies thereafter have demonstrated clinically significant sequelae of inaccurate surgical fusion hardware placement. A number of image guidance systems have been developed to reduce morbidity from hardware malposition in increasingly complex spine surgeries. Advanced image guidance systems such as intraoperative stereotaxis improve the accuracy of pedicle screw placement using a variety of surgical approaches, however their clinical indications and clinical impact remain debated. Beginning with intraoperative fluoroscopy, this article describes the evolution of image guided lumbosacral spinal fusion, emphasizing two-dimensional (2D) and three-dimensional (3D) navigational methods.

A robust and inexpensive phantom for fluoroscopically guided lumbar puncture training.

INTRODUCTION: This report describes the creation process for an inexpensive, durable, lumbar spine phantom for use in fluoroscopically guided lumbar puncture (LP) training. METHODS: The LP phantom prototype was made from a polyvinyl chloride lumbar spine model embedded in a translucent rectangular block of commercially available thermoplastic polymer gel. Radiology residents with limited previous experience performing LP used the phantom for 20 simulated procedures to gain confidence before starting patient procedures. The residents completed surveys detailing their experiences with the phantom. RESULTS: Quantitative evaluation of the phantom using fluoroscopy and computed tomography suggested good physical agreement with human anatomy. Six board-certified radiologists viewed the phantom under live fluoroscopy and indicated that the phantom represented human anatomy with sufficient accuracy. Furthermore, surveys from resident trainees indicated that the thermoplastic tissue substitute simulated the texture and resistance of human soft tissue reasonably well for the purposes of clinical training. The total material cost of the LP phantom prototype was approximately US $148.00. CONCLUSIONS: This novel spine phantom can be produced with relatively low cost when compared with similar commercially available products. The phantom offers reasonable visual and tactile agreement to human anatomy and may be useful for improving the confidence of physician trainees. The LP phantom is durable and can easily be repaired by reheating the polymer tissue substitute.

Simulation-based educational curriculum for fluoroscopically guided lumbar puncture improves operator confidence and reduces patient dose.

RATIONALE AND OBJECTIVES: Fluoroscopically guided lumbar puncture (FGLP) is a commonly performed procedure with increased success rates relative to bedside technique. However, FGLP also exposes both patient and staff to ionizing radiation. The purpose of this study was to determine if the use of a simulation-based FGLP training program using an original, inexpensive lumbar spine phantom could improve operator confidence and efficiency, while also reducing patient dose. MATERIALS AND METHODS: A didactic and simulation-based FGLP curriculum was designed, including a 1-hour lecture and hands-on training with a lumbar spine phantom prototype developed at our institution. Six incoming post-graduate year 2 (PGY-2) radiology residents completed a short survey before taking the course, and each resident practiced 20 simulated FGLPs using the phantom before their first clinical procedure. Data from the 114 lumbar punctures (LPs) performed by the six trained residents (prospective cohort) were compared to data from 514 LPs performed by 17 residents who did not receive simulation-based training (retrospective cohort). Fluoroscopy time (FT), FGLP success rate, and indication were compared. RESULTS: There was a statistically significant reduction in average FT for the 114 procedures performed by the prospective study cohort compared to the 514 procedures performed by the retrospective cohort. This held true for all procedures in aggregate, LPs for myelography, and all procedures performed for a diagnostic indication. Aggregate FT for the prospective group (0.87 ± 0.68 minutes) was significantly lower compared to the retrospective group (1.09 ± 0.65 minutes) and resulted in a 25% reduction in average FT (P = .002). There was no statistically significant difference in the number of failed FGLPs between the two groups. CONCLUSIONS: Our simulation-based FGLP curriculum resulted in improved operator confidence and reduced FT. These changes suggest that resident procedure efficiency was improved, whereas patient dose was reduced. The FGLP training program was implemented by radiology residents and required a minimal investment of time and resources. The LP spine phantom used during training was inexpensive, durable, and effective. In addition, the phantom is compatible with multiple modalities including fluoroscopy, computed tomography, and ultrasound and could be easily adapted to other applications such as facet injections or joint arthrograms.

A Comparison of Techniques for (90)Y PET/CT Image-Based Dosimetry Following Radioembolization with Resin Microspheres.

(90)Y PET/CT following radioembolization has recently been established as a viable diagnostic tool, capable of producing images that are both quantitative and have superior image quality than alternative (90)Y imaging modalities. Because radioembolization is assumed to be a permanent implant, it is possible to convert quantitative (90)Y PET image sets into data representative of spatial committed absorbed-dose. Multiple authors have performed this transformation using dose-point kernel (DPK) convolution to account for the transport of the high-energy (90)Y ß-particles. This article explores a technique called the Local Deposition Method (LDM), an alternative to DPK convolution for (90)Y image-based dosimetry. The LDM assumes that the kinetic energy from each (90)Y ß-particle is deposited locally, within the voxel where the decay occurred. Using the combined analysis of phantoms scanned using (90)Y PET/CT and ideal mathematical phantoms, an accuracy comparison of DPK convolution and the LDM has been performed. Based on the presented analysis, DPK convolution provides no detectible accuracy benefit over the LDM for (90)Y PET-based dosimetry. For PET systems with (90)Y resolution poorer than 3.25 mm at full-width and half-max using a small voxel size, the LDM may produce a dosimetric solution that is more accurate than DPK convolution under ideal conditions; however, image noise can obscure some of the perceived benefit. As voxel size increases and resolution decreases, differences between the LDM and DPK convolution are reduced. The LDM method of post-radioembolization dosimetry has the advantage of not requiring additional post-processing. The provided conversion factors can be used to determine committed absorbed-dose using conventional PET image analysis tools. The LDM is a recommended option for routine post-radioembolization (90)Y dosimetry based on PET/CT imaging.

C-arm rotation as a method for reducing peak skin dose in interventional cardiology.

PURPOSE: Prolonged interventional cardiology (IC) procedures may result in radiation-induced skin injury, a potentially preventable cause of patient morbidity. Rotating the C-arm during an IC procedure may reduce this risk, although the methods by which the technique can be practically applied remains unexplored. A previous study demonstrated that C-arm rotation often increases peak skin dose (PSD) in interventional radiology procedures. The purpose of this study was to determine whether C-arm rotation reduces the PSD in IC procedures and, if so, under what circumstances. MATERIALS AND METHODS: Simulations were performed using a numerical ray-tracing algorithm to analyse the effect of C-arm rotation on PSD across a range of patient sizes, C-arm configurations and procedure types. Specific data from modern fluoroscopes and patient dimensions were used as inputs to the simulations. RESULTS: In many cases, modest C-arm rotation angles completely eliminated overlap between X-ray field sites on the skin. When overlap remained, PSD increases were generally small. One exception was craniocaudal rotation, which tended to increase PSD. C-arm rotation was most effective for large patients and small X-ray field sizes. Small patients may not benefit from C-arm rotation as a procedural modification. The use of a prophylactic method where the C-arm was rotated between small opposing oblique angles was effective in reducing PSD. CONCLUSIONS: With the exception of rotation to steep craniocaudal angles, rotating the C-arm reduces PSD in IC procedures when used as either a procedural modification or a prophylactic strategy. Tight collimation increases the benefit of C-arm rotation.

Radioembolization and the Dynamic Role of (90)Y PET/CT.

Before the advent of tomographic imaging, it was postulated that decay of (90) Y to the 0(+) excited state of (90)Zr may result in emission of a positron-electron pair. While the branching ratio for pair-production is small (~32 × 10(-6)), PET has been successfully used to image (90) Y in numerous recent patients and phantom studies. (90) Y PET imaging has been performed on a variety of PET/CT systems, with and without time-of-flight (TOF) and/or resolution recovery capabilities as well as on both bismuth-germanate and lutetium yttrium orthosilicate (LYSO)-based scanners. On all systems, resolution and contrast superior to bremsstrahlung SPECT has been reported. The intrinsic radioactivity present in LYSO-based PET scanners is a potential limitation associated with accurate quantification of (90) Y. However, intrinsic radioactivity has been shown to have a negligible effect at the high activity concentrations common in (90) Y radioembolization. Accurate quantification is possible on a variety of PET scanner models, with or without TOF, although TOF improves accuracy at lower activity concentrations. Quantitative (90) Y PET images can be transformed into 3-dimensional (3D) maps of absorbed dose based on the premise that the (90) Y activity distribution does not change after infusion. This transformation has been accomplished in several ways, although the most common is with the use of 3D dose-point-kernel convolution. From a clinical standpoint, (90) Y PET provides a superior post-infusion evaluation of treatment technical success owing to its improved resolution. Absorbed dose maps generated from quantitative PET data can be used to predict treatment efficacy and manage patient follow-up. For patients who receive multiple treatments, this information can also be used to provide patient-specific treatment-planning for successive therapies, potentially improving response. The broad utilization of (90) Y PET has the potential to provide a wealth of dose-response information, which may lead to development of improved radioembolization treatment-planning models in the future.

Positron emission tomography/computed tomography in melanoma.

Fludeoxyglucose F 18 positron emission tomography/computed tomography (PET/CT) has been invaluable in the assessment of melanoma throughout the course of the disease. As with any modality, the studies are incomplete and more information will be gleaned as our experience progresses. Additionally, it is hoped that a newer PET agent in the pipeline will give us even greater success in the identification and subsequent treatment of melanoma. This article aims to examine the utilization of PET/CT in the staging, prognostication, and follow-up of melanoma while providing the physicians who order and interpret these studies practical guidelines and interpretive pitfalls.

Role of positron emission tomography/computed tomography in breast cancer.

Although positron emission tomography (PET) imaging may not be used in the diagnosis of breast cancer, the use of PET/computed tomography is imperative in all aspects of breast cancer staging, treatment, and follow-up. PET will continue to be relevant in personalized medicine because accurate tumor status will be even more critical during and after the transition from a generic metabolic agent to receptor imaging. Positron emission mammography is an imaging proposition that may have benefits in lower doses, but its use is limited without new radiopharmaceuticals.