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.

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.

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.

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.

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.

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.

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.

Direct Quantification and Comparison of Intratumoral Hypoxia following Transcatheter Arterial Embolization of VX2 Liver Tumors with Different Diameter Microspheres.

PURPOSE: To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an animal model of liver tumors. MATERIALS AND METHODS: Inoculation of VX2 tumors in the left liver lobe was performed successfully in 12 New Zealand white rabbits weighing 3.7 kg ± 0.5 (mean ± SD). Tumors were deemed eligible for oxygen measurements when the maximum transverse diameter measured 15 mm or more by ultrasound examination. Direct monitoring of oxygenation of implanted rabbit hepatic VX2 tumors was performed with a fiberoptic electrode during and after transarterial embolization of the proper hepatic artery to angiographic flow stasis with microspheres measuring 70-150 µm, 100-300 µm, or 300-500 µm in diameter. RESULTS: Failure to achieve tumor hypoxia as defined despite angiographic flow stasis was observed in 10 of 11 animals. Embolization microsphere size effect failed to demonstrate a significant trend on hypoxia outcome among the diameters tested, and pair-wise comparisons of different embolic diameter treatment groups showed no difference in hypoxia outcome. All microsphere diameters tested resulted in similar absolute reduction (24.3 mm Hg ± 18.3, 29.1 mm Hg ± 1.8, and 19.9 mm Hg ± 9.3, P = .66) and percentage decrease in oxygen (56.0 mm Hg ± 23.9, 56.0 mm Hg ± 6.4, and 35.8 mm Hg ± 20.6, P = .65). Pair-wise comparisons for percent tumor area occupied by embolic agents showed a significantly reduced fraction for 300-500 µm diameters compared with 70-150 µm diameters (P < .05). CONCLUSIONS: In the rabbit VX2 liver tumor model, three tested microsphere diameters failed to cause tumor hypoxia as measured by a fiberoptic probe sensor according to the adopted hypoxia definitions.

Hemispheric asymmetries in cortical and subcortical anatomy.

Previous research studies have reported many hemispherical asymmetries in cortical and subcortical anatomy, but only a subset of findings is consistent across studies. Here, we used improved Freesurfer-based automated methods to analyse the properties of the cortex and seven subcortical structures in 138 young adult subjects. Male and female subjects showed similar hemispheric asymmetries in gyral and sulcal structures, with many areas associated with language processing enlarged in the left hemisphere (LH) and a number of areas associated with visuospatial processing enlarged in the right hemisphere (RH). In addition, we found greater (non-directional) cortical asymmetries in subjects with larger brains. Asymmetries in subcortical structures included larger LH volumes of thalamus, putamen and globus pallidus and larger RH volumes of the cerebellum and the amygdala. We also found significant correlations between the subcortical structural volumes, particularly of the thalamus and cerebellum, with cortical area. These results help to resolve some of the inconsistencies in previous studies of hemispheric asymmetries in brain anatomy.

White matter microstructure throughout the brain correlates with visual imagery in grapheme-color synesthesia.

In this study we show, for the first time, a correlation between the neuroanatomy of the synesthetic brain and a metric that measures behavior not exclusive to the synesthetic experience. Grapheme-color synesthetes (n=20), who experience colors triggered by viewing or thinking of specific letters or numbers, showed altered white matter microstructure, as measured using diffusion tensor imaging, compared with carefully matched non-synesthetic controls. Synesthetes had lower fractional anisotropy and higher perpendicular diffusivity when compared to non-synesthetic controls. An analysis of the mode of anisotropy suggested that these differences were likely due to the presence of more crossing pathways in the brains of synesthetes. Additionally, these differences in white matter microstructure correlated negatively, and only for synesthetes, with a measure of the vividness of their visual imagery. Synesthetes who reported the most vivid visual imagery had the lowest fractional anisotropy and highest perpendicular diffusivity. We conclude that synesthetes as a population vary along a continuum while showing categorical differences in neuroanatomy and behavior compared to non-synesthetes.

Computerized measures of finger tapping: effects of hand dominance, age, and sex.

Computerized measures of digit tapping rate were obtained over 3 successive, 10-sec. periods in the right and left index fingers, from a community sample of 1,519 participants (ages 18 to 65 years; 607 men, 912 women). Differences between the dominant and non-dominant hands were found for tapping rate, movement initiation, and button down times, and the decline in tapping rate over the successive, 10-sec. periods. Declines were found in tapping rate in older participants in association with increased intertap variability. Men had higher tapping rates than women in all age ranges. The computerized finger tapping test is an efficient and precise measure of tapping speed and kinetics of potential utility in research and clinical studies of motor performance.

Radiopaque drug-eluting beads for transcatheter embolotherapy: experimental study of drug penetration and coverage in swine.

PURPOSE: To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70-150 µm or 100-300 µm) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug). MATERIALS AND METHODS: Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of "imageable" DEBs was investigated ex vivo with micro-computed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining. RESULTS: MicroCT demonstrated that 70-150-µm DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (∼300 µm) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70-150-µm DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours. CONCLUSIONS: Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine.

Combination therapy of radiofrequency ablation and bevacizumab monitored with power Doppler ultrasound in a murine model of hepatocellular carcinoma.

PURPOSE: The purpose of this study was to monitor tumour blood flow with power Doppler ultrasound following antiangiogenic therapy with bevacizumab in order to optimally time the application of radiofrequency (RF) ablation to increase ablation diameter. MATERIALS AND METHODS: Athymic nude mice bearing human hepatocellular carcinoma xenografts were treated with bevacizumab and imaged daily with power Doppler ultrasound to quantify tumour blood flow. Mice were treated with RF ablation alone or in combination with bevacizumab at the optimal time, as determined by ultrasound. Ablation diameter was measured with histology and tumour microvascular density was calculated with immunohistochemistry. A computational thermal model of RF ablation was used to estimate ablation volume. RESULTS: A maximum reduction of 27.8 ± 8.6% in tumour blood flow occurred on day 2 following antiangiogenic therapy, while control tumours increased 29.3 ± 17.1% (p < 0.05). Tumour microvascular density was similarly reduced by 45.1 ± 5.9% on day 2 following antiangiogenic therapy. Histology demonstrated a 13.6 ± 5.6% increase in ablation diameter (40 ± 21% increase in volume) consistent with a computational model. CONCLUSION: Quantitative power Doppler ultrasound is a useful biomarker to monitor tumour blood flow following antiangiogenic treatment and to guide the application of RF ablation as a drug plus device combination therapy.

Regional variation, hemispheric asymmetries and gender differences in pericortical white matter.

Brain white matter tissue composition can be quantified using Diffusion Tensor Imaging (DTI) and Magnetization Transfer Imaging (MTI). Fractional Anisotropy (FA), derived from DTI, indexes the integrity, density and organization of axons. Magnetization Transfer Ratio (MTR), derived from MTI, indexes to the presence of cell membranes and myelin. The combined use of FA and MTR provides a more complete picture of white matter structure than either imaging modality in isolation. Here we describe the regional distribution of FA and MTR measurements of pericortical white matter in 56 young, healthy right-handed subjects. Significant regional and lobar differences are seen for both measures along with a significant gender difference in FA. Highly consistent hemispheric asymmetries in FA and MTR were observed, suggesting that the greater fiber coherence and increased myelination of fibers in left hemisphere perisylvian regions may provide a structural basis for left-hemisphere language dominance.

Content and procedural learning in repeated sentence tests of speech perception.

OBJECTIVES: Repeated testing of speech perception is unavoidable in evaluating the benefits of hearing aids and auditory rehabilitation, but procedural and content learning due to repeated test administration can masquerade as a general improvement in speech perception. A previous study of the speech reception threshold (SRT) in quiet reported procedural learning that was sufficiently large to call into question the use of repeated sentence testing in evaluating the effects of auditory rehabilitation. The objective of the first experiment was to measure the effects of content and procedural learning in noise using the Hearing in Noise Test (HINT) when some sentences were repeated and others were not. The objective of the second experiment was to estimate the effects of procedural learning in a larger group of listeners using both the HINT and the Quick Speech in Noise test (QuickSIN) without sentence repetition across test sessions. The objective of the third experiment was to evaluate content learning in the HINT and the QuickSIN when sentence tests were repeated at intervals of several months. DESIGN: In experiment 1, eight normal-hearing listeners completed five 1-hr test sessions on separate days. All sessions included sets of HINT sentences that were presented twice per session to evaluate content learning. Sessions 1 and 5 also included sets of unique sentences to measure procedural learning. In experiment 2, 23 young normal-hearing listeners completed three sessions over a 10-day period with unique HINT and QuickSIN sentence lists presented in each session. In experiment 3, 11 older, normal-hearing listeners completed three sessions of unique HINT and QuickSIN sentence lists, as in experiment 2. After an interval corresponding to a course of auditory rehabilitation training or hearing-aid acclimatization, the listeners were tested with the same sentence lists. RESULTS: In experiment 1, the SRT for repeated sentences improved by an average of 2.7 dB, whereas that for unique sentences showed an insignificant 0.3 dB change. These results demonstrate that HINT SRTs can be affected by content learning for repeated sentences, but are minimally affected by procedural learning for unique sentence material. Significant procedural learning was found only in the first session. In experiment 2, HINT SRTs improved by 0.2 dB per session whereas improvements on the QuickSIN (0.1 dB per session) failed to reach statistical significance. In experiment 3, both tests showed significant improvements; HINT SRTs improved by 0.5 dB and QuickSIN SRTs by 0.4 dB. CONCLUSIONS: Both the HINT and the QuickSIN provide stable and sensitive measures of speech perception across repeated test sessions provided that sentences are not repeated. Practice with at least two sentence lists is needed to eliminate the initial effect of procedural learning in the first session. The results with the HINT and QuickSIN at moderate noise levels differ from previous results of sentence testing in quiet, whereas SRTs improved 6 to 9 dB over five sessions for both repeated and unique sentences. Differences between testing at moderate noise levels and in quiet seem to account for the difference in the stability of these sentence-test measurements.

Consonant identification in consonant-vowel-consonant syllables in speech-spectrum noise.

Identification functions of 20 initial and 20 final consonants were characterized in 9600 randomly sampled consonant-vowel-consonant (CVC) tokens presented in speech-spectrum noise. Because of differences in the response criteria for different consonants, signal detection measures were used to quantify identifiability. Consonant-specific baseline signal-to-noise ratios (SNRs) were adjusted to produce a d(') of 2.20 for each consonant. Consonant identification was measured at baseline SNRs (B), at B-6, and at B+6 dB. Baseline SNRs varied by more than 40 dB for different consonants. Confusion analysis revealed that single-feature place-of-articulation errors predominated at the highest SNR, while combined-feature errors predominated at the lowest SNR. Most consonants were identified at lower SNRs in initial than final syllable position. Vowel nuclei (/a/, /i/, or /u/) significantly influenced the identifiability of 85% of consonants, with consistent vowel effects seen for consonant classes defined by manner, voicing, and place. Manner and voicing of initial and final consonants were processed independently, but place cues interacted: initial and final consonants differing in place of articulation were identified more accurately than those sharing the same place. Consonant identification in CVCs reveals contextual complexities in consonant processing.

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.

Multimodal surface-based morphometry reveals diffuse cortical atrophy in traumatic brain injury.

BACKGROUND: Patients with traumatic brain injury (TBI) often present with significant cognitive deficits without corresponding evidence of cortical damage on neuroradiological examinations. One explanation for this puzzling observation is that the diffuse cortical abnormalities that characterize TBI are difficult to detect with standard imaging procedures. Here we investigated a patient with severe TBI-related cognitive impairments whose scan was interpreted as normal by a board-certified radiologist in order to determine if quantitative neuroimaging could detect cortical abnormalities not evident with standard neuroimaging procedures. METHODS: Cortical abnormalities were quantified using multimodal surfaced-based morphometry (MSBM) that statistically combined information from high-resolution structural MRI and diffusion tensor imaging (DTI). Normal values of cortical anatomy and cortical and pericortical DTI properties were quantified in a population of 43 healthy control subjects. Corresponding measures from the patient were obtained in two independent imaging sessions. These data were quantified using both the average values for each lobe and the measurements from each point on the cortical surface. The results were statistically analyzed as z-scores from the mean with a p < 0.05 criterion, corrected for multiple comparisons. False positive rates were verified by comparing the data from each control subject with the data from the remaining control population using identical statistical procedures. RESULTS: The TBI patient showed significant regional abnormalities in cortical thickness, gray matter diffusivity and pericortical white matter integrity that replicated across imaging sessions. Consistent with the patient's impaired performance on neuropsychological tests of executive function, cortical abnormalities were most pronounced in the frontal lobes. CONCLUSIONS: MSBM is a promising tool for detecting subtle cortical abnormalities with high sensitivity and selectivity. MSBM may be particularly useful in evaluating cortical structure in TBI and other neurological conditions that produce diffuse abnormalities in both cortical structure and tissue properties.

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.