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The concept of overlapping neural networks supporting both speech production and fine motor praxis is well accepted; however, few studies have explored the lateralized behavioral characteristics of both functions when performed simultaneously.This study probes the characteristics of the dominant hemisphere by overloading cognitive processing via a novel dual-task paradigm. In 2 experiments, participants performed sets of motor and speech tasks under single-task and dual-task conditions. The sets of tasks differed as to the extent to which they relied on sequential processing, and we hypothesized that tasks more reliant on this type of processing would suffer a greater performance decrement under dual-task conditions. A reliable measure of hemispheric language dominance was obtained via functional transcranial Doppler (fTCD) ultrasound.Speech production scores in the experimental set (i.e., sequential processing) were consistently impaired under dual-task conditions, a distinction that was not seen in the control set. Results of Experiment 2 confirm those of Experiment 1, whereby speech scores were most strongly impaired under dual-task conditions, especially in the experimental set. Motor performance suffered less than speech performance in dual-task conditions in both the experimental and control sets across both experiments.Data suggest that the common processing capacity for speech and fine motor praxis can be disrupted through a dual-task paradigm. This novel behavioral data supports theories of a motor-based gestural origin for language and indicates that speech production is more sensitive to the effects of increased processing requirements than are motor skills. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Purpose The aim is to investigate whether baseline contrast-enhanced ultrasound (CEUS) correlates with indices of activity in Crohn's disease (CD) and can predict response to medical treatment. Methods In this prospective study, symptomatic CD patients underwent baseline CEUS performed with Definity using both bolus and infusion methods. Time-intensity curves (TIC), peak intensity (PI), and area under curve (AUC) from a region of interest over the diseased bowel were calculated for both bolus and infusion acquisitions. We used Mann-Whitney U test for continuous and chi-square/two-tailed Fisher's exact test for categorical variable comparison and Spearman's correlation coefficient to correlate clinical score and CEUS kinetic parameters. Results Twenty-one patients (9 men, 12 women, median age 32 years) were accrued. Fifteen patients had clinically active disease defined as Harvey-Bradshaw Index (HBI) score ≥5. Median values of baseline CEUS parameters PI (bolus: 26 vs 8.86; P = .023 and perfusion: 7.6 vs 3.2; P = .009) and AUC (bolus: 769 vs 248.8; P = .036 and perfusion: 188.9 vs 73.9; P = .012) differed significantly in patients with active vs inactive disease. Nine patients with active disease underwent escalated or new treatment. Five were nonresponders. Responders had higher median values of baseline parameters (PI, bolus: 35 vs 18.8; P = .556, and perfusion: 7.6 vs 3.9; P = 190), (AUC, bolus: 1473.9 vs 314; P = .111, and perfusion: 154.7 vs 74.4, P = .286). Conclusions CEUS kinetic parameters correlate with clinical and laboratory indices and are significantly higher in patients with active disease. The responders had higher CEUS kinetic parameters than nonresponders that did not reach statistical significance in our small cohort.

To determine if late gadolinium MRI enhancement of colorectal liver metastases (CRCLM) is associated with overall survival among nonsurgical patients. This retrospective study was approved by the institutional research ethics board. Late gadolinium enhancement was measured using target tumour enhancement (TTE) in all nonsurgical patients with CRCLM who received a 10-min delayed phase gadobutrol-enhanced liver MRI between March 1, 2006, and August 31, 2014. A total of 122 patients met inclusion/exclusion criteria. Patients were dichotomized into strong and weak TTE. Kaplan-Meier and Cox regression statistics were used to determine whether TTE was associated with overall survival. Noncontributory potential confounding variables (age, sex, number and size of metastases, carcinoembryonic (CEA) level, and presence of extrahepatic disease) were excluded from the final Cox regression model using the backward Wald elimination. Subgroup Kaplan-Meier survival analyses were performed on patients who were chemotherapy-naive and chemotherapy-treated at the time of MRI. Strong TTE had increased survival compared with those with weak TTE on Kaplan-Meier analysis (2-year survival: 69.8% vs. 43.5%, p = 0.002). Among 96 patients where data was available for multivariable analysis, weak TTE was associated with death (adjusted hazard ratio 0.25, 95% CI 0.11–0.59, p = 0.002), after adjusting for CEA level. Other potential confounders were noncontributory. Subgroup analyses demonstrated that strong TTE had increased survival compared with those with weak TTE in both the chemotherapy-naive (p = 0.047) and chemotherapy-treated (p = 0.008) groups. Strong late gadolinium MRI enhancement of CRCLM is associated with overall survival among nonsurgical patients. • MRI enhancement of colorectal liver metastases is associated with overall survival in nonsurgical patients. • MRI enhancement of colorectal liver metastases is associated with overall survival in both chemotherapy-naive and chemotherapy-treated subgroups.

PURPOSE Adaptive MRI-guided radiotherapy (RT) on a 1.5T-MR-Linac using reduced clinical target volumes (CTV) of 5mm instead of the 15mm standard for glioblastoma (GBM) is currently being evaluated on the UNITED clinical trial (NCT04726397). We explored the morphological changes that occur during adaptive RT with concurrent temozolomide between tumors with MGMT promotor methylation (MGMT-m) vs. unmethylation (MGMT-um). METHODS Thirty patients with IDH-wildtype GBMs were treated with 60Gy in 30 (n=12) or 40Gy in 15 fractions (n=18) (Fx). The CTV included a 5mm expansion on the gross tumor volume (GTV) +/- FLAIR hyperintense areas-at-risk and a 3mm planning target volume. Planning was performed on a pre-treatment reference MRI (FxRef) followed by weekly on-line adaptive re-planning at Fx1, Fx6, etc. acquired on the MR-Linac. Interim fractions were image-guided by pre-beam-on onboard MRI. The GTV/CTVs were quantified by their absolute volumes, volumes relative to the FxRef and the maximum linear distance from the edges of the reference contour to the weekly adapted contours (migration distance, dmig). MGMT promoter methylation status was explored as a fixed effect in a linear mixed statistical model. RESULTS Weekly median changes in GTV relative to FxRef in MGMT-um tumors (n=12) were 10.3%, 9.2%, 10.6%, 14.5%, 18.0% and 17.3%, respectively, while for MGMT-m (n=18) were 3.4%, 0.0%, -8.6%, -11.3%, -11.3% and -5.6% (p=0.021). Between FxRef and Fx1, the GTV increased by over 10% in 58% of MGMT-um tumors vs. 33% of MGMT-m tumors. Similar significant trends were observed with the CTVs. MGMT-um tumors had significantly larger dmig compared to tumors with MGMT-m (median 9.6mm vs. 5.8mm, respectively (p=0.018)). CONCLUSIONS MGMT-um GBM exhibited significant changes in morphology and migration distance between the time of treatment planning to the first treatment fraction, as well as throughout a course of RT. In this population, our results support a greater frequency of imaging and plan adaptation when applying personalized reduced CTV margins.

Multileaf collimator (MLC) linear accelerator (Linac)-based hypofractionated stereotactic radiation therapy (HSRT) is increasingly used not only for large brain metastases or those adjacent to critical structures but also for those metastases that would otherwise be considered for single-fraction radiosurgery (SRS). However, data on outcomes in general are limited, and there is a lack of understanding regarding optimal dosing. Our aim was to report mature image-based outcomes for MLC-Linac HSRT with a focus on clinical and dosimetric factors associated with local failure (LF).A total of 220 patients with 334 brain metastases treated with HSRT were identified. All patients were treated using a 5-fraction daily regimen and were followed with clinical evaluation and volumetric magnetic resonance imaging every 2 to 3 months. Overall survival and progression-free survival were calculated using the Kaplan-Meier method, with LF determined using Fine and Gray's competing risk method. Predictive factors were identified using Cox regression multivariate analysis.Median follow-up was 10.8 months. Median size of treated metastasis was 1.9 cm; 60% of metastases were2 cm in size. The median total dose was 30 Gy in 5 fractions; 36% of the cohort received30 Gy. The median time to LF and 12-month cumulative incidence of LF was 8.5 months and 23.8%, respectively. Median time to death and 12-month overall survival rates were 11.8 months and 48.2%, respectively. Fifty-two metastases (15.6%) had an adverse radiation effect, of which 32 (9.5%) were symptomatic necrosis. Multivariable analysis identified worse LF in patients who received a total dose of30 Gy (hazard ratio, 1.62; P = .03), with LF at 6 and 12 months of 13% and 33% for patients treated with30 Gy versus 5% and 19% for patients treated with30 Gy. Exploratory analysis demonstrated a dose-response effect observed in all histologic types, including among breast cancer subtypes.Optimal local control is achieved with HSRT of ≥30 Gy in 5 daily fractions, independent of tumor volume and histology, with an acceptable risk of radiation necrosis.

PURPOSE/OBJECTIVE(S) The optimal method to evaluate response in neuroendocrine liver metastases (NELM) treated with radiotherapy (RT) is unknown; tumor perfusion parameters were measured by dynamic contrast-enhanced CT and MRI (DCE-CT and -MRI) to evaluate changes with treatment and correlate with efficacy in a pilot study combining everolimus with RT for NELM. MATERIALS/METHODS Fourteen patients with oligoprogressive (< 4) NELM received everolimus (up to a max of 7.5 mg daily) for 28 days prior to, concurrent with, and 14 days following RT. All patients received external-beam RT (30Gy in 10 fractions) or SBRT (up to 60Gy in 3-5 fractions over 1-2 weeks), with the preference for SBRT. Each patient had a DCE-CT and -MRI at baseline (t0), prior to RT (t1) and 7 days after RT (t2). Per lesion response was evaluated by RECIST v1.1. Perfusion parameters of blood flow (BF) and blood volume (BV) by DCE-CT, and the volume transfer constant (Ktrans) and extravascular extracellular space (ve) by DCE-MRI were correlated with the change in size of NELM at the 12-month follow-up (12mo). NELM not treated with RT served as internal controls. Statistics were performed using Wilcoxon Signed-Rank Test and Spearman's coefficient. RESULTS Twenty-one and 14 treated NELM were evaluable by DCE-CT and -MRI respectively. Compared to t0, BV by DCE-CT increased at t1 by 11% (-15, +37%) (median (quartiles)), then significantly decreased after RT from t1 to t2 by -20% (-37, +2%) with P < 0.01. Compared to t0, BF by DCE-CT decreased at t1 by -7% (-25, +33%) and decreased further after RT from t1 to t2 by -13% (-25, +25%) with P = 0.35. Trend of increased BV in internal controls at each time point supports that the effect seen is due to RT. Compared to t1, the decrease in BV by DCE-CT after RT correlated with the max % change in the size of the treated NELM at 12mo (rs = -0.45, P = 0.04). ve by DCE-MRI increased between t0 and t1 from 0.25 (0.21, 0.35) to 0.32 (0.21, 0.42), P = 0.59 and dropped after RT between t1 to t2 to 0.28 (0.21, 0.32) with P = 0.02, whereas ve continued to increase in untreated control data. A similar trend was observed for Ktrans. Conventional ORR was 33%; no progression was seen within 12mo. CONCLUSION Changes in DCE-CT and -MRI are observed in patients receiving everolimus and everolimus+RT for NELM, with BV and ve decreasing significantly post-RT. Given the challenges in assessing response in NELM using traditional RECIST in any context, DCE-CT and -MRI appear to be promising modalities; further studies are required.

Introduction: Liver metastases are common in patients with neuroendocrine neoplasms. The role of stereotactic ablative radiotherapy (SABR) is not well understood in this population. Objective: The objective of this study was to evaluate the safety and efficacy of SABR in treating well-differentiated neuroendocrine liver metastases (WD-NELM). Methods: A retrospective review of patients with WD-NELM treated with SABR was conducted between January 2015 and July 2019. Demographic, treatment, and clinical/radiographic follow-up data were abstracted. RECIST 1.1 criteria were applied to each individual target to evaluate the response to treatment. Local control (LC) and progression-free survival (PFS) were determined using the Kaplan-Meier methodology. Toxicity was reported according to the CTCAE v5.0. Results: Twenty-five patients with a total of 53 liver metastases treated with SABR were identified. Most patients (68%) had midgut tumors, were grade 2 (80%), and had high-volume intrahepatic and/or extrahepatic disease (76%). The median number of liver metastases treated was 2, with a median size of 2.5 cm. The median radiation dose delivered was 50 Gy/5 fractions. The median follow-up was 14 months; 24 of the 25 patients were alive at the time of analysis. The objective response rate was 32%, with improvement or stability in 96% of lesions treated. The median time to best response was 9 months. The 1-year LC and PFS were 92 and 44%, respectively. No grade 3/4 acute or late toxicity was identified. Conclusions: Liver SABR is a safe and promising means of providing LC for WD-NELM. This treatment modality should be evaluated in selected patients in concert with strategies to manage systemic disease.

Liver metastases are common in patients with neuroendocrine tumours. For patients, management must balance disease control with consideration of toxicity, given limited treatment options. Everolimus has demonstrated effectiveness in neuroendocrine neoplasms. Given emerging data of a synergistic effect with radiation therapy, we evaluated combined everolimus and radiation for neuroendocrine liver metastases. This single-arm, single-centre prospective pilot study evaluated the safety and efficacy of combined everolimus and radiotherapy for well-differentiated neuroendocrine liver metastases. Patients with unresectable liver metastases received everolimus for 30 days, followed by concurrent everolimus and liver radiotherapy, then a further 14 days of everolimus. Tolerability was evaluated using the CTCAE v.4.03. Individual metastasis response rate and local control were measured by RECIST v1.1. Overall survival, progression-free survival and freedom from a change in systemic therapy were estimated by the Kaplan–Meier method. Forty metastases were treated in 14 patients. No grade 3 or higher toxicities were identified in the concurrent treatment phase; one patient developed grade 3 toxicity in the post-radiation phase. Overall response rate was 38%. One- and 2-year local control were 97% and 71%. Median progression-free survival was 12 months. One- and 2-year overall survival were 100% and 92%. In conclusion, combined everolimus and radiation are well-tolerated for neuroendocrine liver metastases and are associated with excellent local control. The approach of selective local ablation of oligometastatic or oligoprogressive disease warrants further evaluation in this patient population.

The goal of this study was to evaluate the accuracy of a non-invasive C-plane Doppler estimation of pulsatile blood flow in the lower abdominal vessels of a porcine model. Doppler ultrasound measurements from a matrix array transducer system were compared with invasive volume flow measurements made on the same vessels with a surgically implanted ultrasonic transit-time flow probe. For volume flow rates ranging from 60 to 750 mL/min, agreement was very good, with a Pearson correlation coefficient of 0.97 (p 0.0001) and a mean bias of -4.2%. The combination of 2-D matrix array technology and fast processing gives this Doppler method clinical potential, as many of the user- and system-dependent parameters of previous methods, including explicit vessel angle and diameter measurements, are eliminated.

Highlights • No age effects in direction of speech lateralisation or handedness. • Greater between-hand performance differences evident in younger children. • Atypical speech laterality links to increased motor performance differences., Commonly displayed functional asymmetries such as hand dominance and hemispheric speech lateralisation are well researched in adults. However there is debate about when such functions become lateralised in the typically developing brain. This study examined whether patterns of speech laterality and hand dominance were related and whether they varied with age in typically developing children. 148 children aged 3–10 years performed an electronic pegboard task to determine hand dominance; a subset of 38 of these children also underwent functional Transcranial Doppler (fTCD) imaging to derive a lateralisation index (LI) for hemispheric activation during speech production using an animation description paradigm. There was no main effect of age in the speech laterality scores, however, younger children showed a greater difference in performance between their hands on the motor task. Furthermore, this between-hand performance difference significantly interacted with direction of speech laterality, with a smaller between-hand difference relating to increased left hemisphere activation. This data shows that both handedness and speech lateralisation appear relatively determined by age 3, but that atypical cerebral lateralisation is linked to greater performance differences in hand skill, irrespective of age. Results are discussed in terms of the common neural systems underpinning handedness and speech lateralisation.

The Cognitive Daisy is an innovative assessment system created to provide healthcare staff with an instant snapshot of the cognitive status of older adults in residential care. The Cognitive Daisy comprises a flower head consisting of 15 colour coded petals depicting information about: visual-spatial perception, comprehension, communication, memory and attention. This study confirmed the practicality of the Cognitive Daisy protocol for assessing cognition in a sample of 33 older adults living in residential care and endorsed the use of the Cognitive Daisy as a tool for recognising the cognitive status of care home residents.

A popular scale for assessing knowledge about Alzheimer‘s disease is the Alzheimer‘s Disease Knowledge Scale (ADKS). The aim of the study was to investigate the effect of adding ‗don‘t know‘ to the original ‗true‘ or ‗false‘ response option. It was assumed that this modification would provide insight into the reasons underlying incorrect responses and could distinguish between misconceptions and knowledge gaps. To investigate this, carers (care home carers and informal carers) and members of the general population were recruited. The results showed that percentage correct responses was lower than previously reported, suggesting potential inflation of knowledge by guesses without the ‗don‘t know‘ option. Moreover, care-home workers were more likely to select the incorrect response than ‗don‘t know‘ compared to informal carers for several items related to the earlier stages of AD, suggesting a higher level of misconceptions around this topic and highlighting potential training needs for care home carers.

This study aimed to evaluate the utility of dynamic contrast-enhanced ultrasound (DCE-US) in measuring early tumor response of advanced hepatocellular carcinoma to axitinib. Twenty patients were enrolled (aged 18–78 y; median 65). DCE-US was performed with bolus injection and infusion/disruption replenishment. Median overall survival was 7.1 mo (1.8–27.3) and progression free survival was 3.6 mo (1.8–17.4). Fifteen patients completed infusion scans and 12 completed bolus scans at 2 wk. Among the perfusion parameters, fractional blood volume at infusion (INFBV) decreased at 2 wk in 10/15 (16%–81% of baseline, mean 47%) and increased in 5/15 (116%–535%, mean 220%). This was not significantly associated with progression free survival (p = 0.310) or progression at 16 wk (p = 0.849), but was borderline statistically significant (p = 0.050) with overall survival, limited by a small sample size. DCE-US is potentially useful in measuring early tumor response of advanced hepatocellular carcinoma to axitinib, but a larger trial is needed.

Research using clinical populations to explore the relationship between hemispheric speech lateralization and handedness has focused on individuals with speech and language disorders, such as dyslexia or specific language impairment (SLI). Such work reveals atypical patterns of cerebral lateralization and handedness in these groups compared to controls. There are few studies that examine this relationship in people with motor coordination impairments but without speech or reading deficits, which is a surprising omission given the prevalence of theories suggesting a common neural network underlying both functions. We use an emerging imaging technique in cognitive neuroscience; functional transcranial Doppler (fTCD) ultrasound, to assess whether individuals with developmental coordination disorder (DCD) display reduced left‐hemisphere lateralization for speech production compared to control participants. Twelve adult control participants and 12 adults with DCD, but no other developmental/cognitive impairments, performed a word‐generation task whilst undergoing fTCD imaging to establish a hemispheric lateralization index for speech production. All participants also completed an electronic peg‐moving task to determine hand skill. As predicted, the DCD group showed a significantly reduced left lateralization pattern for the speech production task compared to controls. Performance on the motor skill task showed a clear preference for the dominant hand across both groups; however, the DCD group mean movement times were significantly higher for the non‐dominant hand. This is the first study of its kind to assess hand skill and speech lateralization in DCD. The results reveal a reduced leftwards asymmetry for speech and a slower motor performance. This fits alongside previous work showing atypical cerebral lateralization in DCD for other cognitive processes (e.g., executive function and short‐term memory) and thus speaks to debates on theories of the links between motor control and language production.

Objectives The purpose of this study was to compare the reliability and agreement of 2 methods of 2-dimensional (2D) shear wave elastography (SWE) on liver stiffness in healthy volunteers. We also assessed effects of the prandial state and operator experience on measurements. Methods Two operators, 1 experienced and 1 novice, independently examined 20 healthy volunteers with 2D SWE on 2 ultrasound machines (Aixplorer [SuperSonic Imagine, Aix-en-Provence, France] and Aplio 500 [Canon Medical Systems Corporation, Otawara, Japan]). Volunteers were scanned 8 times by the operators using both machines in fasting and postprandial states. Agreement was evaluated by a Bland-Altman analysis, and the correlation was assessed by the Pearson correlation and intraclass correlation coefficients (ICCs). An analysis of variance was conducted to determine the contribution of the machine, prandial state, and operator experience to the variability. Results Agreement assessed by Bland-Altman plots showed no statistically significant difference in measured liver stiffness between the machines (mean difference, -0.8%; 95% confidence interval, -3.7%, 2.1%), with a critical difference of 1.36 kPa. The correlation was good to excellent for both the crude overall Pearson coefficient and the ICC, both measuring 0.88 (95% confidence interval, 0.82, 0.92). Subclass ICCs for the fasting state, postprandial state, novice operator, and experienced operator were 0.89, 0.88, 0.90, and 0.86, respectively. The 2-way mixed effect analysis of variance showed that the volunteers accounted for 86.3% of variation in median liver stiffness, with no statistically significant contribution from operator experience, the prandial state, or the machine (P = .108, .067, and .296, respectively). Conclusions Our study showed that the 2D SWE techniques had a high degree of reliability and agreement in measurement of liver stiffness in a healthy population. Operator experience and the prandial state did not impart significant variability to stiffness measurements.

A relationship between motor control and speech lateralization has long been postulated by researchers and clinicians with an interest in the functional organization of the human brain. Exactly how motor control might be related to speech representation, however, is rarely examined. This chapter examines current issues relating to the organization, development, and measurement of motor control and speech representation. We further consider from neuropsychological, developmental, neurological, and genetic perspectives that speech and fine motor control involve planning and sequencing processes, which are mediated by an integrated neural network localized to the left hemisphere. Specifically, we discuss studies from our laboratory using functional transcranial Doppler ultrasonography to determine speech laterality, correlating this with hand preference and pegboard measures of motor laterality. Our findings show that handedness, as measured by a motor skill task, can be predictive of speech laterality, both in typically developing adults and children. We have also shown that individuals with developmental motor coordination impairments also show atypical speech lateralization, providing further evidence that neurological motor and speech systems are intrinsically connected. We consider these results in the context of a left-lateralized speech-praxis center model, which could account for the relationship shown between sequence-based motor and speech tasks.

A relationship between motor control and speech lateralization has long been postulated by researchers and clinicians with an interest in the functional organization of the human brain. Exactly how motor control might be related to speech representation, however, is rarely examined. This chapter examines current issues relating to the organization, development, and measurement of motor control and speech representation. We further consider from neuropsychological, developmental, neurological, and genetic perspectives that speech and fine motor control involve planning and sequencing processes, which are mediated by an integrated neural network localized to the left hemisphere. Specifically, we discuss studies from our laboratory using functional transcranial Doppler ultrasonography to determine speech laterality, correlating this with hand preference and pegboard measures of motor laterality. Our findings show that handedness, as measured by a motor skill task, can be predictive of speech laterality, both in typically developing adults and children. We have also shown that individuals with developmental motor coordination impairments also show atypical speech lateralization, providing further evidence that neurological motor and speech systems are intrinsically connected. We consider these results in the context of a left-lateralized speech-praxis center model, which could account for the relationship shown between sequence-based motor and speech tasks.

Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular. This papers reviews the principles and methodology of DCE-US, especially as applied to anti-angiogenic cancer therapies. Reproducibility is an important attribute of such a monitoring method: results are discussed. More recent technical advances in parametric and 3D DCE-US imaging are also summarised and illustrated.

Background Increased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50 mg given for 28 days with a 14-day break (50 mg, 28/14). Methods A single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at≤grade 2. DSM-1 was 50 mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50 mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5 mg with individualized 7-day breaks. DSM-4 was 25 mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables. Results Overall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9–11.9 mo) and overall survival (OS) (23.4–24.5 mo) that was significantly better than the PFS (5.3 mo; P P = 0.03 and 0.003) for the standard schedule (50 mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy. Conclusions Individualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing.

Flat, λ/2-spaced phased arrays for therapeutic ultrasound were examined in silico and in vitro. All arrays were made by combining modules made of 64 square elements with 1.5 mm inter-element spacing along both major axes. The arrays were designed to accommodate integrated, co-aligned diagnostic transducers for targeting and monitoring. Six arrays of 1024 elements (16 modules) and four arrays of 6144 elements (96 modules) were modelled and compared according to metrics such as peak pressure amplitude, focal size, ability to be electronically-steered far off-axis and grating lobe amplitude. Two 1024 element prototypes were built and measured in vitro, producing over 100 W of acoustic power. In both cases, the simulation model of the pressure amplitude field was in good agreement with values measured by hydrophone. Using one of the arrays, it was shown that the peak pressure amplitude dropped by only 24% and 25% of the on-axis peak pressure amplitude when steered to the edge of the array (40 mm) at depths of 30 mm and 50 mm. For the 6144 element arrays studied in in silico only, similarly high steerability was found: even when steered 100 mm off-axis, the pressure amplitude decrease at the focus was less than 20%, while the maximum pressure grating lobe was only 20%. Thermal simulations indicate that the modules produce more than enough acoustic power to perform rapid ablations at physiologically relevant depths and steering angles. Arrays such as proposed and tested in this study have enormous potential: their high electronic steerability suggests that they will be able to perform ablations of large volumes without the need for any mechanical translation.

To identify dynamic contrast-enhanced (DCE) imaging parameters from MRI, CT and US that are prognostic and predictive in patients with metastatic renal cell cancer (mRCC) receiving sunitinib. Thirty-four patients were monitored by DCE imaging on day 0 and 14 of the first course of sunitinib treatment. Additional scans were performed with DCE-US only (day 7 or 28 and 2 weeks after the treatment break). Perfusion parameters that demonstrated a significant correlation (Spearman p < 0.05) with progression-free survival (PFS) and overall survival (OS) were investigated using Cox proportional hazard models/ratios (HR) and Kaplan-Meier survival analysis. A higher baseline and day 14 value for Ktrans (DCE-MRI) and a lower pre-treatment vascular heterogeneity (DCE-US) were significantly associated with a longer PFS (HR, 0.62, 0.37 and 5.5, respectively). A larger per cent decrease in blood volume on day 14 (DCE-US) predicted a longer OS (HR, 1.45). We did not find significant correlations between any of the DCE-CT parameters and PFS/OS, unless a cut-off analysis was used. DCE-MRI, -CT and ultrasound produce complementary parameters that reflect the prognosis of patients receiving sunitinib for mRCC. Blood volume measured by DCE-US was the only parameter whose change during early anti-angiogenic therapy predicted for OS and PFS. • DCE-CT, -MRI and ultrasound are complementary modalities for monitoring anti-angiogenic therapy. • The change in blood volume measured by DCE-US was predictive of OS/PFS. • Baseline vascular heterogeneity by DCE-US has the strongest prognostic value for PFS.

Background: The auditory verbal learning test (AVLT) procedure is routinely deployed in neuropsychological investigations to examine learning and memory status in research and clinical cohorts. Concerns however have been raised regarding the susceptibility of the standard AVLT procedure to ceiling effects, which may have adverse consequences for psychometric properties and result in an underestimation of true potential and differences between normal and abnormal scores. Methods: We examined the performance of patients with temporal lobe epilepsy (TLE; n = 40) who had completed a standard 15-item AVLT and compared a group of TLE patients (n = 12) with healthy controls (n = 12) who completed an extended 24-item AVLT, which was designed to minimise the probability of ceiling scores. Results: Ceiling effects on at least one trial (≥ 14) was achieved by 33% of patients on the 15-item test, with 60% of patients scoring within or above the average list learning total score. Increasing the list length to 24-items reduced the percentage of TLE patients scoring within the normal range to 42%. In addition, no patients but 25% of control participants achieved a maximum score on trial A5. The performance of controls was superior to patients for the best learning trial, learning rate and total learning score. Conclusions: Increasing the list length to 24-items eliminated ceiling scores in all TLE patients and most controls and allowed the true magnitude in difference between the groups to be observed. These findings have implications for decisions relating to optimal AVLT list lengths that might be deployed for memory assessment in TLE.

Thousands of cancer patients are currently in clinical trials evaluating antiangiogenic therapy in the neoadjuvant setting, which is the treatment of localized primary tumors prior to surgical intervention. The rationale is that shrinking a tumor will improve surgical outcomes and minimize growth of occult micrometastatic disease— thus delaying post-surgical recurrence and improving survival. But approved VEGF pathway inhibitors have not been tested in clinically relevant neoadjuvant models that compare pre- and post-surgical treatment effects. Using mouse models of breast, kidney, and melanoma metastasis, we demonstrate that primary tumor responses to neoadjuvant VEGFR TKI treatment do not consistently correlate with improved post-surgical survival, with survival worsened in certain settings. Similar negative effects did not extend to protein-based VEGF pathway inhibitors and could be reversed with altered dose, surgical timing, and treatment duration, or when VEGFR TKIs are combined with metronomic ‘anti-metastatic’ chemotherapy regimens. These studies represent the first attempt to recapitulate the complex clinical parameters of neoadjuvant therapy in mice and identify a novel tool to compare systemic antiangiogenic treatment effects on localized and disseminated disease.

Objective: The determination of speech laterality, especially where it is anomalous, is both a theoretical issue and a practical problem for brain surgery. Handedness is commonly thought to be related to speech representation, but exactly how is not clearly understood. This investigation analyzed handedness by preference rating and performance on a reliable task of motor laterality in 34 patients undergoing a Wada test, to see if they could provide an indicator of speech laterality. Method: Hand usage preference ratings divided patients into left, right, and mixed in preference. Between-hand differences in movement time on a pegboard task determined motor laterality. Results were correlated (χ2) with speech representation as determined by a standard Wada test. Results: It was found that patients whose between-hand difference in speed on the motor task was small or inconsistent were the ones whose Wada test speech representation was likely to be ambiguous or anomalous, whereas all those with a consistently large between-hand difference showed clear unilateral speech representation in the hemisphere controlling the better hand (χ2 = 10.45, df = 1, p < .01, η2 = 0.55) This relationship prevailed across hand preference and level of skill in the hands itself. Conclusion: We propose that motor and speech laterality are related where they both involve a central control of motor output sequencing and that a measure of that aspect of the former will indicate the likely representation of the latter. A between-hand measure of motor laterality based on such a measure may indicate the possibility of anomalous speech representation

It is well established that some individuals present with atypical, non-left hemisphere, cerebral lateralisation for language processing. However previous studies exploring the reliability of functional blood flow responses to detect lateralised activation during speech have focused only on individuals with typical left sided dominance. Here we report test-retest and between-task reliability measures obtained with functional transcranial Doppler ultrasound in 47 participants, including 9 with atypical language presentation. Results showed good test-retest reliability in atypically lateralised individuals, even after an interval of 120 days. Between-task reliability was weaker, but still within acceptable ranges.

Alzheimer's disease (AD) represents one of the most debilitating conditions affecting the elderly. Despite the prevalence and consequences of AD, surveys have revealed that the general public in North America and Australia hold numerous misconceptions of the disease. The aim of this study was to examine whether misconceptions of AD are also endorsed by adults in Britain.The Alzheimer's disease knowledge scale (ADKS) was completed by 312 adults residing in Lincolnshire, UK. The ADKS contains 30 true or false statements pertaining to risk factors, assessment and diagnosis, symptoms, course, life impact, caregiving, and treatment and management of AD.Regardless of age, education, and familiarity with AD, respondents in this survey demonstrated a good understanding (≥80% mean correct) of some items from all categories. However, knowledge gaps exist about the course of the disease, and of conditions that can exacerbate (inadequate nutrition) or simulate (depression) the symptoms of AD. Moreover, a large proportion of respondents (~75%) are unaware that hypertension or hypercholesterolemia may increase ones predisposition to developing AD.Respondents revealed knowledge gaps pertaining to conditions that masquerade as AD, increase ones vulnerability to AD, and exacerbate AD symtomatology. Educational campaigns that specifically target these issues may help reduce the impact of AD.

Innovative imaging approaches for monitoring various types of cancer treatment response are discussed in this paper. Radionuclide imaging has demonstrated favorable capabilities for imaging tumor response based on the binding of radionuclides to the cells responding to the treatment. MRI has recently been utilized for detecting the cellular changes associated with apoptosis. Dynamic contrast-enhanced ultrasound has been proposed for monitoring therapeutics that target blood vessels affecting perfusion. Quantitative ultrasound has been demonstrated to be capable of differentiating between viable cell clusters and clusters responding to treatment. Diffuse optical imaging and photoacoustic imaging have been applied for evaluating functional changes transpiring in soft tissue, such as oxygenation status, during cancer treatment. Considerable developments introduced to improve the precision of treatment response monitoring are expected in the near future to provide clinical approaches to personalized therapy in which therapies can be adapted based on the detection of functional physiology-based responses.

Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.

The relative length of the second and fourth digits (2D:4D ratio) is sexually dimorphic and a retrospective biomarker of prenatal hormonal exposure. Low ratios indicate higher prenatal testosterone (pT) and lower estrogen exposure, whereas the reverse pattern is associated with high ratios. Elevated levels of pT exposure have long been thought to modulate hemispheric specialisation; subsequently many studies use the 2D:4D ratio as a proxy index for pT to examine the effects of prenatal hormonal exposure on lateralised cognitive abilities. Here we used Transcranial Doppler ultrasonography and digit ratio to investigate whether pT has an influence on speech laterality. We tested 34 right and 14 left handed adults. Our results indicate that speech representation is unrelated to digit characteristics and therefore purportedly pT. We discuss these findings in relation to androgen theories of lateralisation.

This study evaluated the impact of different acquisition methods, user-directed region of interest placement and post-processing steps on the quantification of dynamic contrast-enhanced ultrasound measurements of blood volume in 29 patients with renal cancer, pre- and post-treatment. Specifically, we compared tumor quantification using multiple planes versus a single plane, breathhold versus free breathing and large region of interest versus a region targeting the area of highest vascularity. Performance was evaluated using area under the receiver operating characteristic curves to identify the method that best predicts progression-free survival. The intra-class correlation coefficient was also used to investigate how the same parameters affect inter-observer agreement. Of the different methods used to quantify blood volume in this study, the combination that had the highest level of inter-observer agreement (intra-class correlation coefficient = 0.8-0.97) and was the best predictor of progression-free survival was the change in blood volume measured (area under receiver operating characteristic curve = 0.77, p = 0.04) by a multiplane average, acquired during quiet breathing, quantified using a region of interest that encompassed the entire tumor.

PURPOSE The purposes of this study were to establish the physiological interpretation of the shape parameter of the dynamic contrast-enhanced ultrasound (DCE-US) lognormal perfusion model and to evaluate the clinical significance of the parameter in a sample of patients undergoing antiangiogenic therapy for metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS The physiological interpretation of the lognormal shape parameter was explored using computer simulations of disruption-replenishment in fractal models of the microcirculation generated by a piecewise iterative algorithm in MATLAB. Architectural variety was accomplished by introducing random perturbations to the diameter, length, and branching angles to the growing vascular tree. The shape parameter was extracted from the time-intensity curves and compared with the transit time distributions calculated directly from the simulations. Dynamic contrast-enhanced ultrasound data were obtained from 31 consenting patients with mRCC being treated with antiangiogenic therapy. Lognormal parameters related to the blood volume, mean flow speed, and vascular morphology/heterogeneity extracted before, during, and after therapy were correlated with progression-free survival (PFS). Cox proportional hazard ratios were calculated alongside receiver operator characteristics for different combinations of the vascular parameters to determine their ability to distinguish patients who would progress early (less than the median PFS) versus late (greater than the median PFS). RESULTS The lognormal shape parameter correlated strongly to the width of the transit time distribution calculated directly from the simulations, and by extension, to the morphology/heterogeneity of the microvascular network (Spearman r = 0.80, P < 0.001, n = 28). Shorter time to progression was predicted by higher baseline heterogeneity (P = 0.003) and a reduction in tumor blood volume less than 43% (P = 0.002) after 2 weeks of treatment. Combining baseline parameters with changes that occur shortly after starting treatment increased the sensitivity and specificity of DCE-US to identify which patients would progress/resist therapy early versus late compared with when the vascular parameters were considered in isolation. CONCLUSIONS The DCE-US shape parameter from the lognormal perfusion model is representative of microvascular morphology/heterogeneity and may be used to noninvasively characterize the vascular architecture of cancer lesions. A more abnormal flow distribution at baseline predicts for poorer outcome for patients treated with antiangiogenic therapy for metastatic renal cell cancer. Combining pretreatment and on-treatment measurements of vascularity can improve the performance of DCE-US to predict which patients will progress earlier versus later when on antiangiogenic therapy for mRCC.

Increased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50mg given for 28 days with a 14-day break (50mg, 28/14).A single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at ≤ grade 2. DSM-1 was 50mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5mg with individualized 7-day breaks. DSM-4 was 25mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables.Overall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9-11.9 mo) and overall survival (OS) (23.4-24.5 mo) that was significantly better than the PFS (5.3 mo; P0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy.Individualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing.

As a tumor surrogate, the mouse embryo presents as an excellent alternative for examining the binding of angiogenesis-targeting microbubbles and assessing the quantitative nature of molecular ultrasound. We establish the validity of this model by developing a robust method to study microbubble kinetic behavior and investigate the reproducibility of targeted binding in the murine embryo. Vascular endothelial growth factor receptor 2 (VEGFR2)-targeted (MBV), rat immunoglobulin G2 (IgG2) control antibody-targeted (MBC) and untargeted (MBU) microbubbles were introduced into vasculature of living mouse embryos. Non-linear contrast-specific and B-mode ultrasound imaging, performed at 21 MHz with a Vevo-2100 scanner, was used to collect basic perfusion parameters and contrast mean power ratios for all bubble types. We observed a twofold increase (p < 0.001) in contrast mean power ratios for MBV (4.14 ± 1.78) compared with those for MBC (1.95 ± 0.78) and MBU (1.79 ± 0.45). Targeted imaging of endogenous endothelial cell surface markers in mouse embryos is possible with labeled microbubbles. The mouse embryo thus presents as a versatile model for testing the performance of ultrasound molecular targeting, where further development of quantitative imaging techniques may enable rapid evaluations of biomarker expression in studies of vascular development, disease and angiogenesis.

Across different studies, patients with temporal lobe epilepsy (TLE) demonstrate impairments on numerous measures of attentional control that are classically associated with frontal lobe functioning. One aspect of attentional control that has not been examined in TLE is the ability to execute two modality-specific tasks concurrently. We sought to examine the status of dual-task coordination in TLE. We further examined the cohorts' performance on a range of traditional measures of attentional control. Eighteen TLE patients and 22 healthy controls participated in the study. Dual-task performance involved comparing the capacity to execute a tracking and a digit recall task simultaneously with the capacity to execute the tasks separately. We also administered measures of: set shifting (odd-man-out test), sustained attention (elevator counting), selective attention (elevator counting with distraction), and divided attention (trail making test). We found that the proportional decrement in dual-task performance relative to single-task performance did not vary between the groups (TLE = 92.48%; controls = 93.70%), nor was there a significant difference in sustained attention (p > .10). Patients with TLE did demonstrate marked deficits in selective attention (p

This study assessed the reproducibility of shear wave elastography (SWE) in the liver of healthy volunteers. Intra- and inter-operator reliability and repeatability were quantified in three different liver segments in a sample of 15 subjects, scanned during four independent sessions (two scans on day 1, two scans 1 wk later) by two operators. A total of 1440 measurements were made. Reproducibility was assessed using the intra-class correlation coefficient (ICC) and a repeated measures analysis of variance. The shear wave speed was measured and used to estimate Young's modulus using the Supersonics Imagine Aixplorer. The median Young's modulus measured through the inter-costal space was 5.55 ± 0.74 kPa. The intra-operator reliability was better for same-day evaluations (ICC = 0.91) than the inter-operator reliability (ICC = 0.78). Intra-observer agreement decreased when scans were repeated on a different day. Inter-session repeatability was between 3.3% and 9.9% for intra-day repeated scans, compared with to 6.5%–12% for inter-day repeated scans. No significant difference was observed in subjects with a body mass index greater or less than 25 kg/m 2 .

To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US).The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected.In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P.002), with repeated-measure reproducibility of 9%-15%. Significant decreases were also seen with the bolus method, but with poor correlation of changes in bolus peak (r = 0.46, P = .066) and area under the curve (r = 0.47, P = .058), compared with infusion measurements. Changes in DCE US parameters over 2 weeks did not correlate with PFS and could not be used to predict long-term assessment of best response by using RECIST. Follow-up times ranged 28-501 days; the median was 164 days.DCE US provides reproducible and sensitive assessment of vascular changes in response to antiangiogenic therapy. The disruption-replenishment infusion protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome.

Dynamic contrast-enhanced ultrasound (DCE-US) and the method of disruption replenishment has been used for the past 10 years to measure flow noninvasively in the microcirculation. However, the method's perceived poor reproducibility remains a major impediment to widespread clinical acceptance. Poor reproducibility can be attributed, in part, to the curve fitting model that is used to quantify microbubble enhancement. Flow measurement in tumours is further complicated by the spatial and temporal heterogeneity of tumour blood flow. In this work, we evaluate three models of microbubble disruption and replenishment (mono-exponential, a simplified multivessel model by Krix and the lognormal perfusion model) using clinical data (11 patients, 41 sessions) from an antiangiogenic drug trial for metastatic renal cell carcinoma (RCC) and evaluate their contribution to the measurement's variability. Compared with the mono-exponential model, the lognormal perfusion model decreased the variability of intra-session velocity and blood volume measurements by 33% and 34%, respectively. Blood volume assessment using the lognormal perfusion model was comparable to Krix's mutlivessel model. Flow velocity measurement was 18% less variable for the lognormal perfusion model compared with the multivessel model. To further decrease flow measurement variability, we examine a method that exploits microbubble flow dynamics to discard the contribution of flow in large arteries and isolate the portion of the tumour microvasculature that is most sensitive to vessel targeting therapies. The method is validated with an in vitro phantom study prior to its application to the RCC clinical data set. Combined with the lognormal perfusion model, this method decreased the inter-plane variability of clinical measurements of relative tumour blood volume, in some cases by up to 20%.

Surveys have revealed that a high proportion of the public in the US and Canada hold misconceptions pertaining to the sequelae of brain injury. This study examined whether similar misconceptions are endorsed by adults in Britain.Survey.Three hundred and twenty-two participants completed a 17-item questionnaire containing true or false statements about general knowledge of brain injury, coma and consciousness, memory impairments and recovery.Regardless of age, sex, level of education and familiarity with brain injury, participants held mistaken beliefs about consciousness, were inclined to under-estimate the extent of memory deficits and were unaware that patients are more vulnerable and less resistant to further injury. A large proportion of respondents indicated that their knowledge of brain injury had been derived from the popular media.Similar misconceptions to those reported in previous studies exist in Britain. Notably in this study these misconceptions were endorsed by a greater percentage of respondents. Greater public awareness is needed for decisions concerning funding and patient care. It is therefore important for healthcare professionals and public health campaigns to dispel myths about brain injury.

Pseudoenhancement of an avascular region on contrast-enhanced ultrasound often occurs within an echogenic region of a radiofrequency ablation zone due to nonlinear ultrasound propagation through intervening microbubble-perfused tissue. The purpose of this study was to describe the imaging features of this artifact.Twenty-six patients with no tumor recurrence within ablation zones were included. Two radiologists assessed contrast-enhanced ultrasound pseudoenhancement in the arterial (30 seconds), portal (30-90 seconds), and late (90 seconds) phases. If pseudoenhancement was present, the following information was recorded: the degree, time to first appearance, progression over time, and location. The corresponding gray-scale echogenicity (hypo-, iso-, or hyperechoic) and lesion depth were also noted.Fourteen lesions (14/26, 54%) showed pseudoenhancement on contrast-enhanced ultrasound. Fourteen (100%) corresponded to the hyperechoic area within the ablation zone on gray-scale ultrasound and were nonmarginal in location. Pseudoenhancement occurred more frequently in deep lesions (or = 5 cm) than in superficial lesions (5 cm) (p = 0.002). Pseudoenhancement was initiated most frequently in the portal phase (9/14, 64%), followed by the arterial phase (4/14, 29%) and late phase (1/14, 7%). Progression in the degree of pseudoenhancement was shown in most cases (12/14, 86%) and no washout was seen.Pseudoenhancement is frequently seen within ablation zones on contrast-enhanced ultrasound, particularly in deep echogenic lesions. However, pseudoenhancement follows enhancement of the parenchyma between the transducer and target. This observation is consistent with nonlinear propagation of the ultrasound beam, which increases with bubble concentration. Pseudoenhancement shows relatively late initiation, progression over time, and nonmarginal location; these findings are different from those seen in typical tumor recurrence, which shows early enhancement and washout at the margin of the ablation zone.

This study used a guided process-dissociation procedure to examine the contribution of controlled and automatic uses of memory to a cued-recall task in 24 patients with unilateral temporal lobe epilepsy (TLE: 12 left-sided; 12 right-sided), and 12 neurotypical controls. In an inclusion task, participants attempted to complete three-letter word stems using previously studied words, in an exclusion task they aimed to avoid using studied words to complete stems. Patients with left TLE produced fewer target completions under inclusion conditions. Completion rates were not significantly different under exclusion conditions. Estimates derived from process dissociation calculations, confirmed that the cued-recall deficit in left TLE patients arose entirely from impairment in controlled memory processes. There were no group differences in the estimates of automatic processes. Recognition judgements of stems corresponding to studied words did not differ between the groups. Overall the results support the view that controlled and automatic memory processes are mediated by separable neural systems. Hippocampal and related structures within the left MTL are more important than corresponding right hemisphere structures for the controlled retrieval of verbal material. In contrast, the findings from this study do not suggest that the left and right temporal lobes make a differential contribution to automatic memory processing. The theoretical and clinical relevance of these findings are discussed.

Ventricular fibrillation (VF) is the main cause of sudden cardiac death. We hypothesized that VF induced by large scars in an isolated porcine heart model could aid the understanding of VF in human hearts associated with structural disease. The explanted hearts were perfused with blood and Tyrode solution at 37C, and optically imaged with a voltage-sensitive fluorescence dye (di4-ANEPPS excited at 530nm with 150W halogen lamp). The emitted signal was filtered (610nm) and recorded with high speed cameras (MiCAM02, BrainVison, Jp) at 0.7mm spatial resolution. No optical signals could be recorded from the core of chronic infarcts or RF lesions. A total of 10 hearts were used: 4 controls, 3 with lesions generated via RF ablation and 3 with chronic infarcts. We observed the propagation of the depolarization waves and analyzed the VF waveforms at the border zone (BZ) and normal myocardium. We analyzed the VF waves in the frequency domain by calculating the dominant frequency (DF) on select regions of interest using Matlab (Mathworks, Ca). Our results showed that DF is smaller at the BZ compared to healthy tissue. Referenced to the average DF in the control hearts (10.07+/-0.54 Hz), the DF was slightly smaller in healthy myocardium of infarct hearts (i.e., 8.9+/-0.71Hz) and significantly smaller at the border zone (i.e., 6.03 +/- 0.86Hz). In ablated hearts, mean DF in normal myocardium was 9.16+/-0.7Hz and 7.24+/-0.66Hz at BZ, respectively. We suggest that these differences are related to the heterogeneous restitution properties as well as the changes in tissue structure at the BZ. The BZ of chronic scars is comprised of a mixture of viable and necrotic fibers; whereas in the acute settings of RF lesions, inflammation and edema are present at the BZ without alteration of fiber directions.

Contrast-enhanced ultrasound (CEUS) is a promising clinical tool capable of noninvasively quantifying flow and relative vascular volume within the microcirculation. Quantification can be performed by recording the replenishment intensity time course of the imaging plane after the local disruption of agent during a constant infusion. Traditional analyses of the time-intensity curves have relied on mathematical functions (e.g., mono-exponential) that fail to consider the underlying physical principles of the flow system and the influence of the measurement device. In reality, the time-intensity curve reflects the hemodynamics and morphology of the vascular system being measured, the ultrasound field distribution and microbubble properties. We introduce a general analytic disruption replenishment model that attempts to account for these parameters and compare its performance to the established model in a flow phantom. Specifically, the proposed model incorporates the hemodynamic properties of the flow system (velocity distribution and vascular cross section); includes the elevation and axial plane pressure distributions; and accounts for the distinct high and low mechanical index (MI) disruption and detection boundaries. In addition, we demonstrated the importance of the ultrasound beam profile for accurate velocity quantification. It was shown that velocity estimates vary by up to 56% if the depth-dependent elevation thickness is not properly accounted for. Compared with the currently accepted mono-exponential model, the presented formalism was shown to be more robust in the presence of simulated motion artifacts and demonstrated better agreement in both the quality of the fit and estimation of velocity (∼3 to 10% vs. 90% error) for the same flow and acoustic conditions. (E-mail: hudsonjm@gmail.com )

This study examined the contribution of automatic and controlled uses of memory to stem completion in young, middle-aged and older adults, and compared these data with a study involving patients with Alzheimer's disease (AD) who performed the same task (Hudson and Robertson, 2007). In an inclusion task participants aimed to complete three-letter word stems with a previously studied word, in an exclusion task the aim was to avoid using studied words to complete stems. Performances under inclusion and exclusion conditions were contrasted to obtain estimates of controlled and automatic memory processes using process-dissociation calculations (Jacoby, 1991). An age-related decline, evident from middle age was observed for the estimate of controlled processing, whereas the estimate of automatic processing remained invariant across the age groups. This pattern stands in contrast to what is observed in AD, where both controlled and automatic processes have been shown to be impaired. Therefore, the impairment in memory processing on stem completion that is found in AD is qualitatively different from that observed in normal ageing.

This study used the process-dissociation procedure (Jacoby, 1991) to examine the contribution of automatic and controlled uses of memory to a stem completion task in 16 patients with Alzheimer's disease (AD) and a matched group of healthy elderly subjects (EC). In an inclusion task subjects attempted to use a studied word to complete three-letter word stems, in an exclusion task they were instructed to complete stems with unstudied words. Relative to patients with AD, EC subjects produced more target word completions under inclusion conditions, and less target word completions under exclusion conditions. The probability of the AD group using studied words to complete stems was invariant across inclusion and exclusion conditions. Estimates derived from the process-dissociation calculations, showed that the performance of the AD patients was mediated entirely by automatic uses of memory, whereas for EC subjects controlled and automatic processes codetermined task performance. Both estimates of controlled and to a lesser extent automatic uses of memory were greater for the EC than the AD subjects, indicating that the stem completion impairment in AD may not be entirely attributable to a deficiency in controlled memory processes but also due to reduced automatic processing.

11096 Background: Angiogenic cytokines influence tumor growth in mRCC patients (pts) and are modulated by diurnal fluctuations. The timing of antiangiogenic tyrosine kinase inhibitor (TKIs) administration may impact efficacy, toxicity and biomarker expression. Methods: 34 mRCC pts, randomized to receive sunitinib at 8 AM or 8 PM on a 28 days (d) on/14 d off schedule, had blood sampling before and during Rx on the first cycle for potential biomarkers including: sunitinib and metabolite blood levels, 18 circulating angiogenic factors (CAFs) and 4 circulating angiogenic cell types including circulating endothelial cells (CECs). Results: Spearman analysis of the 24 biomarkers obtained on d 14 showed significantly better correlations with OS and PFS in PM-treated pts. Three CAFs in PM-treated pts significantly correlated with both OS and PFS. These included Leptin (r = 0.7182, p = 0.0128 and r = 0.8364, p = 0.0022, respectively), IL-8 (r = -0.635, p = 0.0485 and r = -0.5735, p = 0.031, respectively) and PDGF-β...