Felix Y. Yap

In vitro and in vivo characterization of porous poly-L-lactic acid coatings for subcutaneously implanted glucose sensors

The purpose of this study was to test the hypothesis that porous poly-L-lactic acid (PLLA) sensor coatings reduce fibrosis and promote blood microvessel formation in tissue adjacent to the sensor surface. Porous PLLA coatings were produced using ammonium bicarbonate as the gas foaming/salt leaching agent, and deployed on functional and nonfunctional sensors. The porous coatings minimally affected sensor accuracy and response rate in vitro. Three-week subcutaneous rat studies of nonfunctional glucose sensors showed the anticipated effect of porous coatings enhancing vascularity and decreasing collagen deposition. In contrast, percutaneous functional sensors with and without porous coatings showed no significant difference in terms of histology or sensor response. In spite of the observation that texturing increases the vascularity of the tissue that surrounds implanted sensors, other factors such as the additional mechanical stresses imposed by percutaneous tethering may override the beneficial effects of the porous coatings.

Poly(iohexol) Nanoparticles As Contrast Agents for in Vivo X-ray Computed Tomography Imaging

Biocompatible poly(iohexol) nanoparticles, prepared through cross-linking of iohexol and hexamethylene diisocyanate followed by coprecipitation of the resulting cross-linked polymer with mPEG-polylactide, were utilized as contrast agents for in vivo X-ray computed tomography (CT) imaging. Compared to conventional small-molecule contrast agents, poly(iohexol) nanoparticles exhibited substantially protracted retention within the tumor bed and a 36-fold increase in CT contrast 4 h post injection, which makes it possible to acquire CT images with improved diagnosis accuracy over a broad time frame without multiple administrations.

Current Tumor Ablation Technologies: Basic Science and Device Review

Image-guided tumor ablation is an increasingly utilized tool to treat focal malignancy. Tumor ablation can be divided into two large categories, thermal and chemical ablation. The authors provide an overview of the current methods used to achieve thermal and chemical ablation of tumors, specifically addressing the basic science behind the ablation methods as well as providing a brief synopsis of the commercial devices currently available for use in the United States.

Splenic artery embolization: a single center experience on the safety, efficacy, and clinical outcomes

PURPOSE We aimed to assess the safety, efficacy, and clinical outcomes of splenic artery embolization (SAE). MATERIALS AND METHODS A total of 50 patients (male:female, 33:17; mean age, 49 years) who underwent 50 SAEs between 1998 and 2011 were retrospectively studied. The procedure indications included aneurysm or pseudoaneurysm (n=15), gastric variceal hemorrhage (n=15), preoperative reduction of surgical blood loss (n=9), or other (n=11). In total, 22 procedures were elective, and 28 procedures were urgent or emergent. The embolic agents included coils (n=50), gelatin sponges (n=15), and particles (n=4). The measured outcomes were the technical success of the procedure, efficacy, side effects, and the 30-day morbidity and mortality rates. RESULTS All embolizations were technically successful. The procedure efficacy was 90%; five patients (10%) had a recurrent hemorrhage requiring a secondary intervention. Side effects included hydrothorax (n=26, 52%), thrombocytosis (n=16, 32%), thrombocytopenia (n=13, 26%), and postembolization syndrome (n=11, 22%). Splenic infarcts occurred in 13 patients (26%). The overall and procedure-specific 30-day morbidity rates were 38% (19/50) and 14% (splenoportal thrombosis, 3/50; encapsulated bacterial infection, 1/50; splenic abscess, 1/50; femoral hematoma requiring surgery, 1/50; hydrothorax requiring drainage, 1/50). The overall and procedure-specific 30-day mortality rates were 8% (4/50) and 0%. The multivariate analysis showed that advanced patient age (P = 0.037), postprocedure thrombocytopenia (P = 0.008), postprocedure hydrothorax (P = 0.009), and the need for a secondary intervention (P = 0.004) predicted the 30-day morbidity, while renal insufficiency (P < 0.0001), preprocedure hemodynamic instability (P = 0.044), and preprocedure leukocytosis (P < 0.0001) were prognostic factors for the 30-day mortality. CONCLUSION SAE was performed with high technical success and efficacy, but the outcomes showed nontrivial morbidity rates. Elderly patients with thrombocytopenia and hydrothorax after SAE, and patients who require secondary interventions, should be monitored for complications.

Hypertrophic Osteoarthropathy: Clinical and Imaging Features

Hypertrophic osteoarthropathy (HOA) is a medical condition characterized by abnormal proliferation of skin and periosteal tissues involving the extremities and characterized by three clinical features: digital clubbing (also termed Hippocratic fingers), periostosis of tubular bones, and synovial effusions. HOA can be a primary entity, known as pachydermoperiostosis, or can be secondary to extraskeletal conditions, with different prognoses and management implications for each. There is a high association between secondary HOA and malignancy, especially non-small cell lung cancer. In such cases, it can be considered a form of paraneoplastic syndrome. The most prevalent secondary causes of HOA are pulmonary in origin, which is why this condition was formerly referred to as hypertrophic pulmonary osteoarthropathy. HOA can also be associated with pleural, mediastinal, and cardiovascular causes, as well as extrathoracic conditions such as gastrointestinal tumors and infections, cirrhosis, and inflammatory bowel disease. Although the skeletal manifestations of HOA are most commonly detected with radiography, abnormalities can also be identified with other modalities such as computed tomography, magnetic resonance imaging, and bone scintigraphy. The authors summarize the pathogenesis, classification, causes, and symptoms and signs of HOA, including the genetics underlying the primary form (pachydermoperiostosis); describe key findings of HOA found at various imaging modalities, with examples of underlying causative conditions; and discuss features differentiating HOA from other causes of multifocal periostitis, such as thyroid acropachy, hypervitaminosis A, chronic venous insufficiency, voriconazole-induced periostitis, progressive diaphyseal dysplasia, and neoplastic causes such as lymphoma. ©RSNA, 2016.

Transarterial Sorafenib Chemoembolization: Preliminary Study of Technical Feasibility in a Rabbit Model

PURPOSE To test the feasibility of targeted intraarterial administration of the tyrosine kinase inhibitor chemotherapeutic agent sorafenib to inhibit embolotherapy-induced tumor angiogenesis and reduce systemic drug side effects. MATERIALS AND METHODS The left hepatic lobes of five New Zealand White rabbits (mean weight, 2.7 kg±0.2) were treated with chemoembolization with sorafenib and ethiodized oil emulsion, followed by immediate euthanasia. Postprocedure noncontrast computed tomography (CT) was used to evaluate intrahepatic chemotherapy mixture distribution. Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was then used to directly measure sorafenib concentration in the treated liver tissue. Histopathologic assessment of treated left lobes was performed to identify any immediate toxic effects of the sorafenib solution. RESULTS Lobar sorafenib chemoembolization was successfully performed in all cases via the left hepatic artery. Sorafenib and ethiodized oil (mean, 6.4 mg±3.8 and 0.95 mL±0.7, respectively) were injected, and CT confirmed targeted left hepatic lobe sorafenib emulsion delivery in all cases. Corresponding LC-MS/MS analysis yielded a mean sorafenib concentration of 94.2 μg/mL±48.3 in treated left lobe samples (n = 5), significantly greater than typical therapeutic drug levels (2-10 μg/mL) achieved with oral sorafenib systemic therapy. Histopathologic assessment showed only mild or moderate nonspecific ballooning degeneration in zone 3 hepatocytes, without tissue necrosis. CONCLUSIONS Targeted transarterial sorafenib delivery is feasible and results in higher tissue drug levels than reported for systemic sorafenib therapy, without immediate histopathologic tissue toxicity. Future studies should aim to determine the utility of sorafenib chemoembolization in reducing hypoxia-induced vasculogenesis in liver tumors.

Quantitative Contour Analysis as an Image-based Discriminator Between Benign and Malignant Renal Tumors

OBJECTIVE To investigate whether morphologic analysis can differentiate between benign and malignant renal tumors on clinically acquired imaging. MATERIALS AND METHODS Between 2009 and 2014, 3-dimensional tumor volumes were manually segmented from contrast-enhanced computerized tomography (CT) images from 150 patients with predominantly solid, nonmacroscopic fat-containing renal tumors: 100 renal cell carcinomas and 50 benign lesions (eg, oncocytoma and lipid-poor angiomyolipoma). Tessellated 3-dimensional tumor models were created from segmented voxels using MATLAB code. Eleven shape descriptors were calculated: sphericity, compactness, mean radial distance, standard deviation of the radial distance, radial distance area ratio, zero crossing, entropy, Feret ratio, convex hull area and convex hull perimeter ratios, and elliptic compactness. Morphometric parameters were compared using the Wilcoxon rank-sum test to investigate whether malignant renal masses demonstrate more morphologic irregularity than benign ones. RESULTS Only CHP in sagittal orientation (median 0.96 vs 0.97) and EC in coronal orientation (median 0.92 vs 0.93) differed significantly between malignant and benign masses (P = .04). When comparing these 2 metrics between coronal and sagittal orientations, similar but nonsignificant trends emerged (P = .07). Other metrics tested were not significantly different in any imaging plane. CONCLUSION Computerized image analysis is feasible using shape descriptors that otherwise cannot be visually assessed and used without quantification. Shape analysis via the transverse orientation may be reasonable, but encompassing all 3 planar dimensions to characterize tumor contour can achieve a more comprehensive evaluation. Two shape metrics (CHP and EC) may help distinguish benign from malignant renal tumors, an often challenging goal to achieve on imaging and biopsy.

Safety and efficacy of StarClose SE Vascular Closure System in high-risk liver interventional oncology patients.

Purpose To assess the safety and efficacy of the StarClose SE Vascular Closure System (Abbott Vascular, Abbott Park IL, USA) in high-risk thrombocytopenic and coagulopathic interventional oncology (IO) patients. Methods In this single institution retrospective study, 63 high-risk thrombocytopenic or coagulopathic IO patients (M:F=51:12, mean age 58 years, range 31–88 years) who underwent 83 common femoral arteriotomy closures using the StarClose device were identified among all IO patients (n=131) undergoing StarClose closure (n=177) between 2008–2011. High-risk thrombocytopenia and coagulopathy were defined as platelet count ≤100 103/mL and international normalized ratio (INR) ≥1.5. Procedures included chemoembolization (n=67), radioembolization (n=8), and hepatic arterial mapping with technetium-99m macroaggrated albumin administration (n=8) for treatment of hepatocellular carcinoma (n=79) or liver metastases (n=4). Measured outcomes included technical success of arterial closure and closure-related adverse events, graded according to the Society of Interventional Radiology classification. Results In all cases, 5 French common femoral arterial access was used. Platelet count was ≤100 103/mL in 80/83 (96.4%) cases and INR was ≥1.5 in 35/83 (42.2%) cases. Mean pre-procedure platelet count was 71 (range 26–347) 103/mL and mean INR was 1.4 (range 1.0–2.1). The StarClose device effectively sealed the arteriotomy in 83/83 (100%) cases, 60/83 (72.3%) cases were first-time closures, and 20/83 (24.1%) cases were repeat closures. Small groin hematomas, graded as class A minor complications, developed in 3/83 (3.6%) cases. No other complications were encountered. Conclusions The StarClose SE Vascular Closure System confers high technical success and safety in common femoral arteriotomy closure in high-risk IO patients.

Quantitative morphometric analysis of hepatocellular carcinoma: development of a programmed algorithm and preliminary application.

PURPOSE The quantitative relationship between tumor morphology and malignant potential has not been explored in liver tumors. We designed a computer algorithm to analyze shape features of hepatocellular carcinoma (HCC) and tested feasibility of morphologic analysis. MATERIALS AND METHODS Cross-sectional images from 118 patients diagnosed with HCC between 2007 and 2010 were extracted at the widest index tumor diameter. The tumor margins were outlined, and point coordinates were input into a MATLAB (MathWorks Inc., Natick, Massachusetts, USA) algorithm. Twelve shape descriptors were calculated per tumor: the compactness, the mean radial distance (MRD), the RD standard deviation (RDSD), the RD area ratio (RDAR), the zero crossings, entropy, the mean Feret diameter (MFD), the Feret ratio, the convex hull area (CHA) and perimeter (CHP) ratios, the elliptic compactness (EC), and the elliptic irregularity (EI). The parameters were correlated with the levels of alpha-fetoprotein (AFP) as an indicator of tumor aggressiveness. RESULTS The quantitative morphometric analysis was technically successful in all cases. The mean parameters were as follows: compactness 0.88±0.086, MRD 0.83±0.056, RDSD 0.087±0.037, RDAR 0.045±0.023, zero crossings 6±2.2, entropy 1.43±0.16, MFD 4.40±3.14 cm, Feret ratio 0.78±0.089, CHA 0.98±0.027, CHP 0.98±0.030, EC 0.95±0.043, and EI 0.95±0.023. MFD and RDAR provided the widest value range for the best shape discrimination. The larger tumors were less compact, more concave, and less ellipsoid than the smaller tumors (P < 0.0001). AFP-producing tumors displayed greater morphologic irregularity based on several parameters, including compactness, MRD, RDSD, RDAR, entropy, and EI (P < 0.05 for all). CONCLUSION Computerized HCC image analysis using shape descriptors is technically feasible. Aggressively growing tumors have wider diameters and more irregular margins. Future studies will determine further clinical applications for this morphologic analysis.

Fast Fourier transform-based analysis of renal masses on contrast-enhanced computed tomography images for grading of tumor

Purpose: Evaluate the feasibility of spectral analysis, particularly fast fourier transform (FFT), to help clinicians differentiate clear cell renal cell carcinoma (ccRCC) tumor grades using contrast-enhanced computed tomography (CECT) images of renal masses, quantitatively, and compare their performance to the Fuhrman grading system. Materials and Methods: Regions of interest of the whole lesion were manually segmented and co-registered from multiphase CT acquisitions of 95 patients with ccRCC. Here, FFT is employed to objectively quantify the texture of a tumor surface by evaluating tissue gray-level patterns and automatically measure frequency-based texture metrics. An independent t-test or a Wilcoxon rank sum test (depending on the data distribution) was used to determine if the spectral analysis metrics would produce statistically significant differences between the tumor grades. Receiver operating characteristic (ROC) curve analysis was used to evaluate the usefulness of spectral metrics in predicting the ccRCC grade. Results: The Wilcoxon test showed that there was a significant difference in complexity index between the different tumor grades, p < 0.01 at all the four phases of CECT acquisition. In all cases a positive correlation was observed between tumor grade and complexity index. ROC analysis revealed the importance of the entropy of FFT amplitude, FFT phase and complexity index and its ability to identify grade 1 and grade 4 tumors from the rest of the population. Conclusion: Our study suggests that FFT-based spectral metrics can differentiate between ccRCC grades, and in combination with other metrics improve patient management and prognosis of renal masses.