Woodchuck Hepatic Anatomy and Vascular Alterations Due to Hepatocellular Carcinoma with Angiographic Atlas of the Abdomen and Pelvis.

PURPOSE: To characterize the hepatic and abdominal angiographic anatomy of woodchucks and vascular changes associated with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-nine woodchucks (23 with viral-associated HCC, 6 without) underwent multiphasic computed tomography (CT). Fourteen woodchucks (8 with HCC) also underwent diagnostic angiography. Hepatic arterial diameters were measured on the CT scans. Woodchucks were divided into 3 groups: non-tumor-bearing, largest tumor supplied by the right hepatic artery (RHA), and largest tumor supplied by the left hepatic artery (LHA). Statistical analysis with a repeated measures model was performed to determine the effects of tumor location (right, left), vessel measured (RHA, LHA), and interaction between the 2 on vessel diameter. Lobar arteries supplying HCC were compared with those that did not. RESULTS: CT anatomy and normal and variant vascular anatomy were defined. In woodchucks with HCC, LHA and RHA supplying tumors had mean diameters of 2.0 mm ± 0.3 and 1.6 mm ± 0.3 versus 1.5 mm ± 0.3 and 1.1 mm ± 0.2 for non-tumor-supplying arteries (P = .0002 and P < .0001), respectively. Lobar arteries supplying tumors were similarly ectatic. The right lateral lobe artery had the most profound increase in the mean diameter when supplying tumors, measuring 1.7 mm ± 0.1 versus 1.0 mm ± 0.1 in the non-tumor-supplying artery (P < .0001). There were no differences in the diameters of the aorta and celiac, common, and proper hepatic arteries between tumor- and non-tumor-bearing woodchucks. An angiographic atlas of the abdominal vessels was generated. CONCLUSIONS: HCC tumoral vasculature in woodchucks was ectatic compared with normal vasculature. This phenomenon recapitulates human HCC and may facilitate investigation of transcatheter and drug delivery therapies in an HCC animal model.

Monopolar Radiofrequency Energy Delivered by a Conductive Endovascular Basket or Guidewire Leads to Thermal Occlusion in a Swine Model.

PURPOSE: To assess the feasibility of inducing vascular occlusion by application of radiofrequency (RF) energy via conductive endovascular wires or baskets. MATERIALS AND METHODS: A retrievable nitinol basket and stainless steel guidewire with a platinum tip were evaluated as conductors for endovascular application of RF energy. Tissue-mimicking thermochromic gel phantoms that change color with heating were cast with 2-, 5-, and 7-mm-diameter lumens and filled with 37 oC saline. After ablation, the phantoms were sectioned, and the thermal footprints were evaluated. Six castrated male domestic swine underwent endovascular ablation using the basket in iliac arteries and guidewires in renal arteries. Post-procedural angiography was performed, and postmortem arterial segments were resected for histopathologic analysis. RESULTS: In the phantom, the depth of thermal change in the 5- and 7-mm lumens averaged 6.3 and 6.0 mm along the basket, respectively, and in the 2- and 5-mm lumens, the depth of thermal change averaged 1.9 and 0.5 mm along the wire, respectively. In the swine, RF energy delivery led to angiographic occlusion at 12 of 13 sites. Thermal injury and occlusion were similar at the proximal, middle, and distal basket treatment zone, whereas injury and occlusion decreased from the proximal to the distal end of the 5-cm wire treatment zone. CONCLUSIONS: Endovascular delivery of RF energy via a conductive basket in medium-sized arteries or a guidewire in small arteries led to acute angiographic and histologic occlusion. The potential to induce stasis might be useful in settings where rapid occlusion is desirable.

Safety and Tolerability of Topotecan-Eluting Radiopaque Microspheres for Hepatic Chemoembolization in a Rabbit Preclinical Model.

PURPOSE: Topotecan is a camptothecin analogue with potential advantages over irinotecan for transarterial chemoembolization (TACE) of hepatic colorectal metastases including greater anti-neoplastic activity without enzymatic activation. The purpose of this study was to assess safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered by TACE in a rabbit model and to compare the in vitro elution of topotecan from microspheres to irinotecan. MATERIALS AND METHODS: Topotecan was loaded into radiopaque microspheres (70-150 µm, DC Bead LUMI™, Biocompatibles UK Ltd-Boston Scientific Corporation) to the maximum capacity of 80 mg/mL of microspheres. Six healthy New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis. Assessment of toxicities included regular liver function tests and complete blood counts until euthanasia 28 days post-TACE. In vitro topotecan elution from the microspheres was assessed using an open-loop flow-through system and compared to irinotecan. RESULTS: The mean bead volume and topotecan dose delivered were 0.086 mL (0.076-0.105 mL) and 1.99 mg/kg (1.51-2.55 mg/kg), respectively. Aspartate aminotransferase and alanine aminotransferase were elevated post-embolization but resolved within 2 weeks. One rabbit died two days after TACE with pyloric duodenal perforation observed at necropsy, potentially due to non-target embolization. In vitro elution of topotecan from ROMTOP was complete in 10 h compared to 3 h for irinotecan-loaded microspheres. CONCLUSION: Selective embolization with ROMTOP was tolerated at a dose of 2 mg/kg (24 mg/m2) in rabbits. In vitro topotecan elution from microspheres was more prolonged compared to irinotecan.

Transarterial Chemoembolization in a Woodchuck Model of Hepatocellular Carcinoma.

PURPOSE: To assess the feasibility of transarterial chemoembolization with drug-eluting embolic (DEE) microspheres in a woodchuck model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Nine woodchucks were studied: 4 normal animals and 5 animals infected with woodchuck hepatitis virus in which HCC had developed. Three animals with HCC underwent multidetector CT. A 3-F sheath was introduced into the femoral artery, and the hepatic arteries were selectively catheterized with 2.0-2.4-F microcatheters. Normal animals underwent diagnostic angiography and bland embolization. Animals with HCC underwent DEE transarterial chemoembolization with 70-150-µm radiopaque microspheres loaded with 37.5 mg doxorubicin per milliliter. Cone-beam CT and multidetector CT were performed. Following euthanasia, explanted livers underwent micro-CT, histopathologic examination, and fluorescence imaging of doxorubicin. RESULTS: The tumors were hypervascular and supplied by large-caliber tortuous vessels, with arteriovenous shunts present in 2 animals. There was heterogeneous enhancement on multidetector CT with areas of necrosis. Six tumors were identified. The most common location was the right medial lobe (n = 3). Mean tumor volume was 30.7 cm3 ± 12.3. DEE chemoembolization of tumors was achieved. Excluding the 2 animals with arteriovenous shunts, the mean volume of DEE microspheres injected was 0.49 mL ± 0.17. Fluorescence imaging showed diffusion of doxorubicin from the DEE microspheres into the tumor. CONCLUSIONS: Woodchuck HCC shares imaging appearances and biologic characteristics with human HCC. Selective catheterization and DEE chemoembolization may similarly be performed. Woodchucks may be used to model interventional therapies and possibly characterize radiologic-pathologic correlations.

Accessible continued professional development for maternal mental health.

BACKGROUND:  Changing global health and development trends have resulted in a need for continued professional development (CPD) within the health and development sectors. In low-resource settings, where the need for training and CPD may be highest, there are significant challenges for disseminating information and skills. There is a need to improve mental health literacy and reduce levels of stigma about maternal mental illness. The Bettercare series of distance learning books provides a peer-based format for CPD. We aimed to evaluate the Bettercare Maternal Mental Health book as a format for CPD. AIM:  The aim of this study was to determine whether the Bettercare Maternal Mental Health book significantly improves knowledge and decreases stigma around mental health for care providers from the health and social development sectors. SETTING:  One hundred and forty-one participants (social workers, nursing students and health professionals) were provided with the Bettercare Maternal Mental Health book to study. METHODS:  Before and after studying the book, the same multiple-choice knowledge test and the Mental Illness Clinicians' Attitude Scale were used to assess cognitive knowledge and mental health stigma, respectively. RESULTS:  Participants' knowledge showed a statistically significant (p < 0.001) improvement between the pre- and post-test results, for all six chapters of the book. However, participants' attitudes towards mental illness did not show a statistically significant change between the pre- and post-test results. CONCLUSION:  We found that this method of learning elicited significant improvement in mental health knowledge for care providers. Continued professional development policy planners and curriculum developers may be interested in these findings.

Feasibility and Acute Safety Study of Radiofrequency Energy Delivery to the Vena Caval Wall via an IVC Filter in Swine.

Retrievable inferior vena cava (IVC) filters are self-expanding metallic devices implanted in the IVC to prevent migration of thrombi from the deep veins of the legs and pelvis to the lungs. The risk of complications from the filters increases with duration of implantation, but retrieval may be difficult due to intimal hyperplasia around the components of the filter. In this study, the potential for delivery of radiofrequency (RF) energy to the IVC wall via the filter was investigated. IVC filters were deployed in 4 swine while attached to a snare connected to a 480 kHz RF generator. Energy ranging from 0 to 48 kJ was applied via the filter followed by re-sheathing and withdrawal of the filter while connected to a force measurement device. Resheathing forces for the 0-energy cohort and pooled data from the 6-24 kJ cohorts were 4.50±0.70 N and 4.50±0.75 N, respectively. Petechial hemorrhages and variable non-occlusive thrombi were noted in some cohorts including the 0-energy cohort, consistent with delivery and acute retrieval of an IVC filter. Histologically, the extent of RF-induced injury was subtle at 6 kJ with focal areas of homogenized collagen while the 12 kJ cohort showed segmental tissue charring with coagulation necrosis which was more extensive for the 24 kJ cohort. The 48 kJ energy caused more extensive and non-target organ damage. The study demonstrated feasibility of delivery of RF to the IVC wall via a deployed filter, supporting further study of the ability of local RF heating of the IVC wall to inhibit the neointimal hyperplasia or as an aid in retrieval.

The Dyad-Adaptive Paced Auditory Serial Addition Test (DA-PASAT): Normative data and the effects of repeated testing, simulated malingering, and traumatic brain injury.

The Paced Auditory Serial Addition Test (PASAT) is widely used to evaluate processing speed and executive function in patients with multiple sclerosis, traumatic brain injury, and other neurological disorders. In the PASAT, subjects listen to sequences of digits while continuously reporting the sum of the last two digits presented. Four different stimulus onset asynchronies (SOAs) are usually tested, with difficulty increasing as SOAs are reduced. Ceiling effects are common at long SOAs, while the digit delivery rate often exceeds the subject's processing capacity at short SOAs, causing some subjects to stop performing altogether. In addition, subjects may adopt an "alternate answer" strategy at short SOAs, which reduces the test's demands on working-memory and processing speed. Consequently, studies have shown that the number of dyads (consecutive correct answers) is a more sensitive measure of PASAT performance than the overall number of correct sums. Here, we describe a 2.5-minute computerized test, the Dyad-Adaptive PASAT (DA-PASAT), where SOAs are adjusted with a 2:1 staircase, decreasing after each pair of correct responses and increasing after misses. Processing capacity is reflected in the minimum SOA (minSOA) achieved in 54 trials. Experiment 1 gathered normative data in two large populations: 1617 subjects in New Zealand ranging in age from 18 to 65 years, and 214 Californians ranging in age from 18 to 82 years. Minimum SOAs were influenced by age, education, and daily hours of computer-use. Minimum SOA z-scores, calculated after factoring out the influence of these factors, were virtually identical in the two control groups, as were response times (RTs) and dyad ratios (the proportion of hits occurring in dyads). Experiment 2 measured the test-retest reliability of the DA-PASAT in 44 young subjects who underwent three test sessions at weekly intervals. High intraclass correlation coefficients (ICCs) were found for minSOAs (0.87), response times (0.76), and dyad ratios (0.87). Performance improved across test sessions for all measures. Experiment 3 investigated the effects of simulated malingering in 50 subjects: 42% of simulated malingerers produced abnormal (p< 0.05) minSOA z-scores. Simulated malingerers with abnormal scores were distinguished with 87% sensitivity and 69% specificity from control subjects with abnormal scores by excessive differences between training performance and the actual test. Experiment 4 investigated patients with traumatic brain injury (TBI): patients with mild TBI performed within the normal range while patients with severe TBI showed deficits. The DA-PASAT reduces the time and stress of PASAT assessment while gathering sensitive measures of dyad processing that reveal the effects of aging, malingering, and traumatic brain injury on performance.

Distribution and Detection of Radiopaque Beads after Hepatic Transarterial Embolization in Swine: Cone-Beam CT versus MicroCT.

PURPOSE: To determine the true distribution of radiopaque beads (ROBs) after hepatic embolization in swine as imaged by micro-computed tomography (microCT) compared with in vivo cone-beam computerized tomography (CT) imaged at different kVp settings. MATERIALS AND METHODS: Swine (n = 3) underwent hepatic transarterial embolization (n = 6) with the use of 70-150-µm ROBs under fluoroscopic guidance. After stasis, in vivo cone-beam CT was performed at 120, 100, and 80 kVp. The animal was euthanized, the liver resected, and microCT with 17 µm resolution performed on embolized tissue samples. The resulting cone-beam CT and microCT data were segmented and registered. Total vessel length, minimum volume-enclosing ellipsoid (MVEE), and number of independent volumes were measured. Maximum-intensity projections (MIPs) were generated for each cone-beam CT. RESULTS: Metrics for all cone-beam CT segmentations differed significantly from microCT segmentations. Segmentations at 80 kVp presented significantly greater vessel length, MVEE, and number of independent volumes compared with 100 kVp and 120 kVp. In addition, 100 kVp segmentations presented significantly greater vessel length than 120 kVp. MIPs presented greater visualization than cone-beam CT segmentations and improved as kVp decreased. CONCLUSIONS: The full ROB distribution was more extensive than was apparent on cone-beam CT. Quantitative measures of embolic distribution demonstrated significantly better correlation with microCT with decreasing kVp. Similarly, qualitative analysis of MIPs showed improved visualization of beads with decreasing kVp. These findings demonstrate the clinical value of 80 kVp and 100 kVp protocols in the imaging of radiopaque embolizations compared with 120 kVp. However, considerations on X-ray penetration and dose may favor use of 100 kVp imaging over 80 kVp.

Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI™.

We have developed a straightforward and efficient method of introducing radiopacity into Polyvinyl alcohol (PVA)-2-Acrylamido-2-methylpropane sulfonic acid (AMPS) hydrogel beads (DC Bead™) that are currently used in the clinic to treat liver malignancies. Coupling of 2,3,5-triiodobenzaldehyde to the PVA backbone of pre-formed beads yields a uniformly distributed level of iodine attached throughout the bead structure (~150mg/mL) which is sufficient to be imaged under standard fluoroscopy and computed tomography (CT) imaging modalities used in treatment procedures (DC Bead LUMI™). Despite the chemical modification increasing the density of the beads to ~1.3g/cm3 and the compressive modulus by two orders of magnitude, they remain easily suspended, handled and administered through standard microcatheters. As the core chemistry of DC Bead LUMI™ is the same as DC Bead™, it interacts with drugs using ion-exchange between sulfonic acid groups on the polymer and the positively charged amine groups of the drugs. Both doxorubicin (Dox) and irinotecan (Iri) elution kinetics for all bead sizes evaluated were within the parameters already investigated within the clinic for DC Bead™. Drug loading did not affect the radiopacity and there was a direct relationship between bead attenuation and Dox concentration. The ability (Dox)-loaded DC Bead LUMI™ to be visualized in vivo was demonstrated by the administration of into hepatic arteries of a VX2 tumor-bearing rabbit under fluoroscopy, followed by subsequent CT imaging.

Accessible continued professional development for maternal mental health

Background: Changing global health and development trends have resulted in a need for continued professional development (CPD) within the health and development sectors. In low-resource settings, where the need for training and CPD may be highest, there are significant challenges for disseminating information and skills. There is a need to improve mental health literacy and reduce levels of stigma about maternal mental illness. The Bettercare series of distance learning books provides a peer-based format for CPD. We aimed to evaluate the Bettercare Maternal Mental Health book as a format for CPD. Aim: The aim of this study was to determine whether the Bettercare Maternal Mental Health book significantly improves knowledge and decreases stigma around mental health for care providers from the health and social development sectors.Setting: One hundred and forty-one participants (social workers, nursing students and health professionals) were provided with the Bettercare Maternal Mental Health book to study.Methods: Before and after studying the book, the same multiple-choice knowledge test and the Mental Illness Clinicians' Attitude Scale were used to assess cognitive knowledge and mental health stigma, respectively.Results: Participants' knowledge showed a statistically significant (p < 0.001) improvement between the pre- and post-test results, for all six chapters of the book. However, participants' attitudes towards mental illness did not show a statistically significant change between the pre- and post-test results. Conclusion: We found that this method of learning elicited significant improvement in mental health knowledge for care providers. Continued professional development policy planners and curriculum developers may be interested in these findings

Computerized Analysis of Verbal Fluency: Normative Data and the Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury.

In verbal fluency (VF) tests, subjects articulate words in a specified category during a short test period (typically 60 s). Verbal fluency tests are widely used to study language development and to evaluate memory retrieval in neuropsychiatric disorders. Performance is usually measured as the total number of correct words retrieved. Here, we describe the properties of a computerized VF (C-VF) test that tallies correct words and repetitions while providing additional lexical measures of word frequency, syllable count, and typicality. In addition, the C-VF permits (1) the analysis of the rate of responding over time, and (2) the analysis of the semantic relationships between words using a new method, Explicit Semantic Analysis (ESA), as well as the established semantic clustering and switching measures developed by Troyer et al. (1997). In Experiment 1, we gathered normative data from 180 subjects ranging in age from 18 to 82 years in semantic ("animals") and phonemic (letter "F") conditions. The number of words retrieved in 90 s correlated with education and daily hours of computer-use. The rate of word production declined sharply over time during both tests. In semantic conditions, correct-word scores correlated strongly with the number of ESA and Troyer-defined semantic switches as well as with an ESA-defined semantic organization index (SOI). In phonemic conditions, ESA revealed significant semantic influences in the sequence of words retrieved. In Experiment 2, we examined the test-retest reliability of different measures across three weekly tests in 40 young subjects. Different categories were used for each semantic ("animals", "parts of the body", and "foods") and phonemic (letters "F", "A", and "S") condition. After regressing out the influences of education and computer-use, we found that correct-word z-scores in the first session did not differ from those of the subjects in Experiment 1. Word production was uniformly greater in semantic than phonemic conditions. Intraclass correlation coefficients (ICCs) of correct-word z-scores were higher for phonemic (0.91) than semantic (0.77) tests. In semantic conditions, good reliability was also seen for the SOI (ICC = 0.68) and ESA-defined switches in semantic categories (ICC = 0.62). In Experiment 3, we examined the performance of subjects from Experiment 2 when instructed to malinger: 38% showed abnormal (p< 0.05) performance in semantic conditions. Simulated malingerers with abnormal scores could be distinguished with 80% sensitivity and 89% specificity from subjects with abnormal scores in Experiment 1 using lexical, temporal, and semantic measures. In Experiment 4, we tested patients with mild and severe traumatic brain injury (mTBI and sTBI). Patients with mTBI performed within the normal range, while patients with sTBI showed significant impairments in correct-word z-scores and category shifts. The lexical, temporal, and semantic measures of the C-VF provide an automated and comprehensive description of verbal fluency performance.

Review of the 2015 Guidelines for Maternity Care with relevance to congenital disorders.

The 4th edition of the Guidelines for Maternal Care in South Africa published by the National Department of Health in 2015 was evaluated with relevance to the care and prevention of congenital disorders (CDs). Disparate terminology is used for CDs throughout the guidelines, and overall less detail is included on CDs compared with the previous edition. This demonstrates a lack of awareness around the growing health need and contribution of CDs to the disease burden in South Africa (SA). Referrals to medical genetic services in the guidelines for mothers of advanced maternal age and other high-risk categories do not take into account the insufficient capacity available for screening and diagnosis of CDs. This highlights the lack of consultation with the medical genetics sector during the development of the guidelines. To respond to the Sustainable Development Goals by 2030, CDs must be integrated comprehensively at all levels of healthcare in SA.

A Computerized Test of Design Fluency.

Tests of design fluency (DF) assess a participant's ability to generate geometric patterns and are thought to measure executive functions involving the non-dominant frontal lobe. Here, we describe the properties of a rapidly administered computerized design-fluency (C-DF) test that measures response times, and is automatically scored. In Experiment 1, we found that the number of unique patterns produced over 90 s by 180 control participants (ages 18 to 82 years) correlated with age, education, and daily computer-use. Each line in the continuous 4-line patterns required approximately 1.0 s to draw. The rate of pattern production and the incidence of repeated patterns both increased over the 90 s test. Unique pattern z-scores (corrected for age and computer-use) correlated with the results of other neuropsychological tests performed on the same day. Experiment 2 analyzed C-DF test-retest reliability in 55 participants in three test sessions at weekly intervals and found high z-score intraclass correlation coefficients (ICC = 0.79). Z-scores in the first session did not differ significantly from those of Experiment 1, but performance improved significantly over repeated tests. Experiment 3 investigated the performance of Experiment 2 participants when instructed to simulate malingering. Z-scores were significantly reduced and pattern repetitions increased, but there was considerable overlap with the performance of the control population. Experiment 4 examined performance in veteran patients tested more than one year after traumatic brain injury (TBI). Patients with mild TBI performed within the normal range, but patients with severe TBI showed reduced z-scores. The C-DF test reliably measures visuospatial pattern generation ability and reveals performance deficits in patients with severe TBI.

Microvascular Perfusion Changes following Transarterial Hepatic Tumor Embolization.

PURPOSE: To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. MATERIALS AND METHODS: Rabbit Vx2 liver tumors were embolized with 100-300-µm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3-5 per group; 18 total). RESULTS: Mean microvascular density was 70 vessels/mm(2) ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31(+) structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. CONCLUSIONS: Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy.

An improved spatial span test of visuospatial memory.

In the widely used Corsi Block Test and Wechsler Spatial Span Tests, participants must reproduce sequences of blocks in the order touched by the examiner until two trials are missed at the same sequence length. The examiner records either the maximum number of blocks correctly reported or the total number of correct lists. Here, we describe a computerized spatial span test (C-SST) that uses psychophysical procedures to quantify visuospatial mean span (MnS) with sub-digit precision. Results from 187 participants ranging in age from 18 to 82 years showed that accuracy declined gradually with list length around the MnS (by ∼30% per item). Simulation studies revealed high variance and biases in CBT and Wechsler measures, and demonstrated that the C-SST provided the most accurate estimate of true span (i.e., the sequence length producing 50% correct). MnS declined more rapidly with age than mean digit span (MnDS) measured in the same participants. Response times correlated with both MnS and MnDS scores. Error analysis showed that omission and transposition errors predominated, with weaker primacy and recency effects in spatial span than digit span testing. The C-SST improves the precision of spatial span testing and reveals significant differences between visuospatial and verbal working memory.

Preparation of Radiopaque Drug-Eluting Beads for Transcatheter Chemoembolization.

PURPOSE: To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo. MATERIALS AND METHODS: An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model. RESULTS: Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology. CONCLUSIONS: A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.

Multimodality Imaging of Ethiodized Oil-loaded Radiopaque Microspheres during Transarterial Embolization of Rabbits with VX2 Liver Tumors.

Purpose To assess the visibility of radiopaque microspheres during transarterial embolization (TAE) in the VX2 rabbit liver tumor model by using multimodality imaging, including single-snapshot radiography, cone-beam computed tomography (CT), multidetector CT, and micro-CT. Materials and Methods The study was approved by the institutional animal care and use committee. Fifteen VX2-tumor-bearing rabbits were assigned to three groups depending on the type of embolic agent injected: 70-150-µm radiopaque microspheres in saline (radiopaque microsphere group), 70-150-µm radiopaque microspheres in contrast material (radiopaque microsphere plus contrast material group), and 70-150-µm radiolucent microspheres in contrast material (nonradiopaque microsphere plus contrast material group). Rabbits were imaged with single-snapshot radiography, cone-beam CT, and multidetector CT. Three to 5 weeks after sacrifice, excised livers were imaged with micro-CT and histologic analysis was performed. The visibility of the embolic agent was assessed with all modalities before and after embolization by using a qualitative three-point scale score reading study and a quantitative assessment of the signal-to-noise ratio (SNR) change in various regions of interest, including the tumor and its feeding arteries. The Kruskal-Wallis test was used to compare the rabbit characteristics across groups, and the Wilcoxon signed rank test was used to compare SNR measurements before and after embolization. Results Radiopaque microspheres were qualitatively visualized within tumor feeding arteries and targeted tissue with all imaging modalities (P < .05), and their presence was confirmed with histologic examination. SNRs of radiopaque microsphere deposition increased after TAE on multidetector CT, cone-beam CT, and micro-CT images (P < .05). Similar results were obtained when contrast material was added to radiopaque microspheres, except for additional image attenuation due to tumor enhancement. For the group with nonradiopaque microspheres and contrast material, retained tumoral contrast remained qualitatively visible with all modalities except for micro-CT, which demonstrated soluble contrast material washout over time. Conclusion Radiopaque microspheres were visible with all imaging modalities and helped increase conspicuity of the tumor as well as its feeding arteries after TAE in a rabbit VX2 liver tumor model. (©) RSNA, 2015.

The Bay Area Verbal Learning Test (BAVLT): Normative Data and the Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury.

Verbal learning tests (VLTs) are widely used to evaluate memory deficits in neuropsychiatric and developmental disorders. However, their validity has been called into question by studies showing significant differences in VLT scores obtained by different examiners. Here we describe the computerized Bay Area Verbal Learning Test (BAVLT), which minimizes inter-examiner differences by incorporating digital list presentation and automated scoring. In the 10-min BAVLT, a 12-word list is presented on three acquisition trials, followed by a distractor list, immediate recall of the first list, and, after a 30-min delay, delayed recall and recognition. In Experiment 1, we analyzed the performance of 195 participants ranging in age from 18 to 82 years. Acquisition trials showed strong primacy and recency effects, with scores improving over repetitions, particularly for mid-list words. Inter-word intervals (IWIs) increased with successive words recalled. Omnibus scores (summed over all trials except recognition) were influenced by age, education, and sex (women outperformed men). In Experiment 2, we examined BAVLT test-retest reliability in 29 participants tested with different word lists at weekly intervals. High intraclass correlation coefficients were seen for omnibus and acquisition scores, IWIs, and a categorization index reflecting semantic reorganization. Experiment 3 examined the performance of Experiment 2 participants when feigning symptoms of traumatic brain injury. Although 37% of simulated malingerers showed abnormal (p < 0.05) omnibus z-scores, z-score cutoffs were ineffective in discriminating abnormal malingerers from control participants with abnormal scores. In contrast, four malingering indices (recognition scores, primacy/recency effects, learning rate across acquisition trials, and IWIs) discriminated the two groups with 80% sensitivity and 80% specificity. Experiment 4 examined the performance of a small group of patients with mild or severe TBI. Overall, both patient groups performed within the normal range, although significant performance deficits were seen in some patients. The BAVLT improves the speed and replicability of verbal learning assessments while providing comprehensive measures of retrieval timing, semantic organization, and primacy/recency effects that clarify the nature of performance.

The Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury on Visual Choice Reaction Time.

Choice reaction time (CRT), the time required to discriminate and respond appropriately to different stimuli, is a basic measure of attention and processing speed. Here, we describe the reliability and clinical sensitivity of a new CRT test that presents lateralized visual stimuli and adaptively adjusts stimulus onset asynchronies using a staircase procedure. Experiment 1 investigated the test-retest reliability in three test sessions performed at weekly intervals. Performance in the first test session was accurately predicted from age and computer-use regression functions obtained in a previously studied normative cohort. Central processing time (CentPT), the difference between the CRTs and simple reaction time latencies measured in a separate experiment, accounted for 55% of CRT latency and more than 85% of CRT latency variance. Performance improved significantly across the three test sessions. High intraclass correlation coefficients were seen for CRTs (0.90), CentPTs (0.87), and an omnibus performance measure (0.81) that combined CRT and minimal SOA z-scores. Experiment 2 investigated performance in the same participants when instructed to feign symptoms of traumatic brain injury (TBI): 87% produced abnormal omnibus z-scores. Simulated malingerers showed greater elevations in simple reaction times than CRTs, and hence reduced CentPTs. Latency-consistency z-scores, based on the difference between the CRTs obtained and those predicted based on CentPT latencies, discriminated malingering participants from controls with high sensitivity and specificity. Experiment 3 investigated CRT test performance in military veterans who had suffered combat-related TBI and symptoms of post-traumatic stress disorder, and revealed small but significant deficits in performance in the TBI population. The results indicate that the new CRT test shows high test-retest reliability, can assist in detecting participants performing with suboptimal effort, and is sensitive to the effects of TBI on the speed and accuracy of visual processing.

The Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury on High-Precision Measures of Simple Visual Reaction Time.

Simple reaction time (SRT), the latency to respond to a stimulus, has been widely used as a basic measure of processing speed. In the current experiments, we examined clinically-relevant properties of a new SRT test that presents visual stimuli to the left or right hemifield at varying stimulus onset asynchronies (SOAs). Experiment 1 examined test-retest reliability in 48 participants who underwent three test sessions at weekly intervals. In the first test, log-transformed (log-SRT) z-scores, corrected for the influence of age and computer-use, were well predicted by regression functions derived from a normative population of 189 control participants. Test-retest reliability of log-SRT z-scores was measured with an intraclass correlation coefficient (ICC = 0.83) and equaled or exceeded those of other SRT tests and other widely used tests of processing speed that are administered manually. No significant learning effects were observed across test sessions. Experiment 2 investigated the same participants when instructed to malinger during a fourth testing session: 94% showed abnormal log-SRT z-scores, with 83% producing log-SRT z-scores exceeding a cutoff of 3.0, a degree of abnormality never seen in full-effort conditions. Thus, a log-SRT z-score cutoff of 3.0 had a sensitivity (83%) and specificity (100%) that equaled or exceeded that of existing symptom validity tests. We argue that even expert malingerers, fully informed of the malingering-detection metric, would be unable to successfully feign impairments on the SRT test because of the precise control of SRT latencies that would be required. Experiment 3 investigated 26 patients with traumatic brain injury (TBI) tested more than 1 year post-injury. The 22 patients with mild TBI showed insignificantly faster SRTs than controls, but a small group of four patients with severe TBI showed slowed SRTs. Simple visual reaction time is a reliable measure of processing speed that is sensitive to the effects of malingering and TBI.