Bad habits-good goals? Meta-analysis and translation of the habit construct to alcoholism.

Excessive alcohol consumption remains a global public health crisis, with millions suffering from alcohol use disorder (AUD, or simply "alcoholism"), leading to significantly reduced life expectancy. This review examines the interplay between habitual and goal-directed behaviors and the associated neurobiological changes induced by chronic alcohol exposure. Contrary to a strict habit-goal dichotomy, our meta-analysis of the published animal experiments combined with a review of human studies reveals a nuanced transition between these behavioral control systems, emphasizing the need for refined terminology to capture the probabilistic nature of decision biases in individuals with a history of chronic alcohol exposure. Furthermore, we distinguish habitual responding from compulsivity, viewing them as separate entities with diverse roles throughout the stages of the addiction cycle. By addressing species-specific differences and translational challenges in habit research, we provide insights to enhance future investigations and inform strategies for combatting AUD.

Cost-effectiveness of stress CTP versus CTA in detecting obstructive CAD or in-stent restenosis in stented patients.

OBJECTIVES: The aim of this retrospective study was to determine cost-effectiveness of stress myocardial CT perfusion (CTP), coronary CT angiography (CTA), and the combination of both in suspected obstructive coronary artery disease (CAD) or in-stent restenosis (ISR) in patients with previous coronary stent implantation. METHODS: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with CTA, CTP, and CTA + CTP. Model input parameters were obtained from published literature. Probabilistic sensitivity analysis was performed to evaluate overall model uncertainty. A single-variable deterministic sensitivity analysis evaluated the sensitivity of the results to plausible variations in model inputs. Cost-effectiveness was assessed based on a cost-effectiveness threshold of $100,000 per QALY. RESULTS: In the base-case scenario with willingness to pay of $100,000 per QALY, CTA resulted in total costs of $47,013.87 and an expected effectiveness of 6.84 QALYs, whereas CTP resulted in total costs of $46,758.83 with 6.93 QALYs. CTA + CTP reached costs of $47,455.63 with 6.85 QALYs. Therefore, strategies CTA and CTA + CTP were dominated by CTP in the base-case scenario. Deterministic sensitivity analysis demonstrated robustness of the model to variations of diagnostic efficacy parameters and costs in a broad range. CTP was cost-effective in the majority of iterations in the probabilistic sensitivity analysis as compared with CTA. CONCLUSIONS: CTP is cost-effective for the detection of obstructive CAD or ISR in patients with previous stenting and therefore should be considered a feasible approach in daily clinical practice. KEY POINTS: • CTP provides added diagnostic value in patients with previous coronary stents. • CTP is a cost-effective method for the detection of obstructive CAD or ISR in patients with previous stenting.

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder.

RATIONALE: Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES: In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS: Out of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS: The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS: Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Creating high-quality radiology reports in foreign languages through multilingual structured reporting.

OBJECTIVES: Globalization and migration are increasing the demand for reports in different languages. We aimed to examine if structured reports created by non-German-speaking radiologists with multilingual templates show significant differences in quality to structured reports and free-text reports by German native speakers. METHODS: We used structured templates that allow radiologists to report in their mother tongue and then switch the report language to German or English automatically using proprietary software. German- and English-speaking radiology residents created structured reports in both German and English with these templates. Reports for three different exam types were created (intensive care chest x-ray, shoulder x-ray specifically for degenerative processes, and CT pulmonary angiogram for pulmonary embolism). The report quality of automatically translated German structured reports by English-speaking radiologists and German structured reports by German radiologists was then evaluated by German clinicians with a standardized questionnaire. The questionnaire was designed to assess attributes including content, comprehensibility, clinical consequences, and overall quality. RESULTS: Structured reports by English-speaking radiologists that were automatically translated into German and German structured reports by German radiologists both received very high or high overall quality ratings in the majority of cases, showing no significant differences in quality. Likewise, no significant differences were observed between the two report types regarding comprehensibility and clinical consequences. Structured reports by German radiologists received significantly better ratings for overall quality and comprehensibility compared to free-text reports by German radiologists. CONCLUSIONS: Multilingual structured reporting templates may serve as a feasible tool for creating high-quality radiology reports in foreign languages. KEY POINTS: • Multilingualism in structured reporting templates can be a useful tool for creating high-quality radiology reports in foreign languages. • German reports created with multilingual structured reporting templates by English-speaking radiologists and German structured reports by German radiologists exhibit no significant differences in overall report quality. • Multilingual structured reporting templates can help radiologists overcome communication barriers and facilitate teleradiology.

Targeted overexpression of CRH receptor subtype 1 in central amygdala neurons: effect on alcohol-seeking behavior.

RATIONALE: The corticotropin-releasing hormone (CRH) system is a key mediator of stress-induced responses in alcohol-seeking behavior. Recent research has identified the central nucleus of the amygdala (CeA), a brain region involved in the regulation of fear and stress-induced responses that is especially rich in CRH-positive neurons, as a key player in mediating excessive alcohol seeking. However, detailed characterization of the specific influences that local neuronal populations exert in mediating alcohol responses is hampered by current limitations in pharmacological and immunohistochemical tools for targeting CRH receptor subtype 1 (CRHR1). OBJECTIVE: In this study, we investigated the effect of cell- and region-specific overexpression of CRHR1 in the CeA using a novel transgenic tool. METHODS: Co-expression of CRHR1 in calcium-calmodulin-dependent kinase II (αCaMKII) neurons of the amygdala was demonstrated by double immunohistochemistry using a Crhr1-GFP reporter mouse line. A Cre-inducible Crhr1-expressing adeno-associated virus (AAV) was site-specifically injected into the CeA of αCaMKII-CreERT2 transgenic rats to analyze the role of CRHR1 in αCaMKII neurons on alcohol self-administration and reinstatement behavior. RESULTS: Forty-eight percent of CRHR1-containing cells showed co-expression of αCaMKII in the CeA. AAV-mediated gene transfer in αCaMKII neurons induced a 24-fold increase of Crhr1 mRNA in the CeA which had no effect on locomotor activity, alcohol self-administration, or cue-induced reinstatement. However, rats overexpressing Crhr1 in the CeA increased responding in the stress-induced reinstatement task with yohimbine serving as a pharmacological stressor. CONCLUSION: We demonstrate that CRHR1 overexpression in CeA-αCaMKII neurons is sufficient to mediate increased vulnerability to stress-triggered relapse into alcohol seeking.

Reprogramming of mPFC transcriptome and function in alcohol dependence.

Despite its limited immediate reinforcement value, alcohol has a potent ability to induce neuroadaptations that promote its incentive salience, escalation of voluntary alcohol intake and aversion-resistant alcohol seeking. A constellation of these traits, collectively called 'post-dependent', emerges following brain exposure to repeated cycles of intoxication and withdrawal. The medial prefrontal cortex (mPFC) and its subdivisions exert top-down regulation of approach and avoidance behaviors, including those that lead to alcohol intake. Here, we review an emerging literature which indicates that a reprogramming of mPFC function occurs with prolonged exposure of the brain to cycles of alcohol intoxication and withdrawal. This reprogramming results in molecular dysregulations that contribute to the post-dependent syndrome. Convergent evidence has identified neuroadaptations resulting in altered glutamatergic and BDNF-mediated signaling, and for these pathways, direct evidence for a mechanistic role has been obtained. Additional evidence points to a dysregulation of pathways involving calcium homeostasis and neurotransmitter release. Recent findings indicate that global DNA hypermethylation is a key factor in reprogramming the mPFC genome after a history of dependence. As one of the results of this epigenetic remodeling, several histone modifying epigenetic enzymes are repressed. Among these, PR-domain zinc-finger protein 2, a methyltransferase that selectively mono-methylates histone H3 at lysine 9 has been functionally validated to drive several of the molecular and behavioral long-term consequences of alcohol dependence. Information processing within the mPFC involves formation of dynamic neuronal networks, or functional ensembles that are shaped by transcriptional responses. The epigenetic dysregulations identified by our molecular studies are likely to alter this dynamic processing in multiple ways. In summary, epigenetic molecular switches in the mPFC appear to be turned on as alcoholism develops. Strategies to reverse these processes may offer targets for disease-modifying treatments.

A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology.

It has been proposed that vulnerability to nicotine addiction is moderated by variation at the µ-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 polymorphism rs1799971_A>G (A118G). Here we use this model system together with a cohort of German youth to examine the role of the OPRM1 A118G variation on nicotine reward. Nicotine reinforcement was examined in the humanized mouse model using i.v. self-administration. Male (n=17) and female (n=26) mice homozygous either for the major human A allele (AA) or the minor G allele (GG) underwent eight daily 2 h sessions of nicotine self-administration. Furthermore, male (n=104) and female (n=118) subjects homozygous for the A allele or carrying the G allele from the Mannheim Study of Children at Risk were evaluated for pleasurable and unpleasant experiences during their initial smoking experience. A significant sex-by-genotype effect was observed for nicotine self-administration. Male 118GG mice demonstrated higher nicotine intake than male 118AA mice, suggesting increased nicotine reinforcement. In contrast, there was no genotype effect in female mice. Human male G allele carriers reported increased pleasurable effects from their first smoking experience, as compared to male homozygous A, female G and female homozygous A allele carriers. The 118G allele appears to confer greater sensitivity to nicotine reinforcement in males, but not females.

Prediction of Stent-Retriever Thrombectomy Outcomes by Dynamic Multidetector CT Angiography in Patients with Acute Carotid T or MCA Occlusions.

BACKGROUND AND PURPOSE: The selection of patients for endovascular therapy is an important issue in stroke imaging. The aim of this study was to determine the predictive value of 3 different dynamic CT angiography parameters, occlusion length, collateralization extent, and time delay to maximum enhancement, for latest generation of stent retriever thrombectomy recanalization outcomes in patients with acute ischemic stroke. MATERIALS AND METHODS: In this study, subjects were selected from an initial cohort of 2059 consecutive patients who had undergone multiparametric CT, including whole-brain CT perfusion. We included all patients with a complete occlusion of the M1 segment of the MCA or the carotid T and subsequent intra-arterial stent retriever thrombectomy. Dynamic CT angiography was reconstructed from whole-brain CT perfusion raw datasets. Angiographic outcome was scored by using the modified TICI scale; and clinical outcome, by using the modified Rankin Scale. Logistic regression analyses were performed to determine independent predictors of a favorable angiographic (mTICI = 3) and clinical outcome (mRS ≤2). RESULTS: Sixty-nine patients (mean age, 68 ± 14 years; 46% men) were included for statistical analysis. In the regression analysis, a short occlusion length was an independent predictor of favorable angiographic outcome (OR, 0.41; P < .05). Both collateralization grade (OR, 1.00; P > .05) and time delay to peak enhancement (OR, 0.90; P > .05) failed to predict a favorable angiographic outcome. None of the dynamic CT angiography predictors were significantly associated with clinical outcome on discharge (OR, 0.664-1.011; P = .330-.953) or at 90 days (OR, 0.779-1.016; P = .130-.845). CONCLUSIONS: A short occlusion length as determined by dynamic CT angiography is an independent predictor of a favorable angiographic outcome of stent retriever thrombectomy in patients with ischemic stroke.

Strategies of collateral blood flow assessment in ischemic stroke: prediction of the follow-up infarct volume in conventional and dynamic CTA.

BACKGROUND AND PURPOSE: Collateral blood flow is an important prognostic marker in the acute stroke situation but approaches for assessment vary widely. Our aim was to compare strategies of collateral blood flow assessment in dynamic and conventional CTA in their ability to predict the follow-up infarction volume. MATERIALS AND METHODS: We retrospectively included all patients with an M1 occlusion from an existing cohort of 1912 consecutive patients who underwent initial multimodal stroke CT and follow-up MR imaging or nonenhanced CT. Collateralization was assessed in both conventional CT angiography and dynamic CT angiography by using 3 different collateral grading scores and segmentation of the volume of hypoattenuation. Arterial, arteriovenous, and venous phases were reconstructed for dynamic CT angiography, and all collateral scores and the volume of hypoattenuation were individually assessed for all phases. Different grading systems were compared by using the Bayesian information criterion calculated for multivariate regression analyses (Bayesian information criterion difference = 2-6, "positive"; Bayesian information criterion difference = 6-10, "strong"; Bayesian information criterion difference = >10, "very strong"). RESULTS: One hundred thirty-six patients (mean age, 70.4 years; male sex, 41.2%) were included. In the multivariate analysis, models containing the volume of hypoattenuation showed a significantly better model fit than models containing any of the 3 collateral grading scores in conventional CT angiography (Bayesian information criterion difference = >10) and dynamic CT angiography (Bayesian information criterion difference = >10). All grading systems showed the best model fit in the arteriovenous phase. For the volume of hypoattenuation, model fit was significantly higher for models containing the volume of hypoattenuation as assessed in the arteriovenous phase of dynamic CT angiography compared with the venous phase (Bayesian information criterion difference = 6.2) and the arterial phase of dynamic CT angiography (Bayesian information criterion difference = >10) and in comparison with conventional CT angiography (Bayesian information criterion difference = >10). CONCLUSIONS: The use of dynamic CT angiography within the arteriovenous phase by using quantification of the volume of hypoattenuation is the superior technique for assessment of collateralization among the tested approaches.

Value of high resolution compression elastography and color doppler sonography in characterisation of breast lesions: comparison of different high-frequency transducers.

PURPOSE: To evaluate the additional effect of higher frequent linear probes than 12.5 MHz in color Doppler sonography and free hand sonoelastography of benign and malignant breast masses and to compare different color encodings in sonoelastography. MATERIALS AND METHODS: From December 2012 to March 2013, 37 patients with benign or malignant breast masses were prospectively included in this study. All solid masses have been histologically proven. Two readers assessed sonoelastographic findings at 12.5 MHz vs. 17 MHz according to the tsukuba elasticity score and additionally different color encodings were compared. Results of Doppler sonography using a score of 0, 1 or 2, depending on the degree of perfusion, also were assessed at 12.5 MHz vs. 17 MHz. RESULTS: Among the 37 examined breast masses there were 10 cysts, 16 fibroadenomas and 11 carcinomas. Median participant age was 49.0 years. Use of color Doppler sonography enabled to distinguish cysts from solid breast masses (p < 0.001), without an improvement at 17 MHz. Additional sonoelastography significantly improved the specificity in solid breast masses (p < 0.001). No changes could be seen using different colors in sonoelastography. CONCLUSION: Combination of color Doppler sonography and sonoelastography can increase the accuracy in distinguishing benign from malignant breast masses. The use of linear probes with a higher frequency than 12.5 MHz does not show any benefit, neither in color Doppler sonography nor in sonoelastography.

[Computed tomography angiography as the basis for optimized therapy planning before endovascular aneurysm repair (EVAR)]. / CT-Angiographie als Grundlage der optimierten Therapieplanung vor endovaskulärer Aneurysmaausschaltung (EVAR).

Computed tomography angiography (CTA) of the aorta is an accepted standard diagnostic procedure for preoperative evaluation and planning of endovascular treatment of abdominal aortic aneurysms (endovascular aortic repair EVAR). The CTA method delivers all relevant anatomical and morphological information on the underlying pathology of the aorta and pelvic axes. Various software solutions are available for multiplanar reconstruction of the CT data for exact measurement of the access routes and landing zones and are essential components of individualized operation planning. The synthesis of all CT-based information allows a safe and exactly targeted release of the stent graft in the aorta. Furthermore, the periprocedural radiation dose can be reduced by a precise preoperative planning of the positions to be irradiated during implantation.

Coordinated dysregulation of mRNAs and microRNAs in the rat medial prefrontal cortex following a history of alcohol dependence.

Long-term changes in brain gene expression have been identified in alcohol dependence, but underlying mechanisms remain unknown. Here, we examined the potential role of microRNAs (miRNAs) for persistent gene expression changes in the rat medial prefrontal cortex (mPFC) after a history of alcohol dependence. Two-bottle free-choice alcohol consumption increased following 7-week exposure to intermittent alcohol intoxication. A bioinformatic approach using microarray analysis, quantitative PCR (qPCR), bioinformatic analysis and microRNA-messenger RNA (mRNA) integrative analysis identified expression patterns indicative of a disruption in synaptic processes and neuroplasticity. About 41 rat miRNAs and 165 mRNAs in the mPFC were significantly altered after chronic alcohol exposure. A subset of the miRNAs and mRNAs was confirmed by qPCR. Gene ontology categories of differential expression pointed to functional processes commonly associated with neurotransmission, neuroadaptation and synaptic plasticity. microRNA-mRNA expression pairing identified 33 miRNAs putatively targeting 89 mRNAs suggesting transcriptional networks involved in axonal guidance and neurotransmitter signaling. Our results demonstrate a significant shift in microRNA expression patterns in the mPFC following a history of dependence. Owing to their global regulation of multiple downstream target transcripts, miRNAs may have a pivotal role in the reorganization of synaptic connections and long-term neuroadaptations in alcohol dependence. MicroRNA-mediated alterations of transcriptional networks may be involved in disrupted prefrontal control over alcohol drinking observed in alcoholic patients.

Benefit of contrast enhanced ultrasound for detection of ischaemic lesions and arterio venous fistulas in renal transplants - a feasibility study.

PURPOSE: To evaluate the benefit of CEUS (contrast enhanced ultrasound) regarding depiction of ischaemic lesions and AVFs (arterio venous fistula) in renal transplants compared to standard ultrasound (US) (grey-scale and color Doppler). MATERIALS AND METHODS: In this study 22 patients suspected of having acute vascular complication after renal transplantation were investigated using standard ultrasound (grey-scale US and color Doppler US) and CEUS, respectively. Validity of the respective US-techniques regarding depiction of ischaemic lesions and AVF was compared. Dynamic CTA (computed tomography angiography) served as the standard of reference. RESULTS: In 10 renal transplants arterial embolism associated with kidney infarctions were observed. Very good correlation to dynamic CTA was yielded using CEUS, whereas grey scale US and color Doppler US was limited in the accurate depiction of renal infarctions. Additionally CEUS was superior in displaying arteriovenous fistulas compared to standard US. CONCLUSION: CEUS as a fast and bedside available imaging modality not associated with dose exposure or renal toxicity facilitates improved detection of ischaemic lesions and AVFs compared to standard US and thus should be considered for short term follow up of renal transplants.

Improved carotid atherosclerotic plaques imaging with contrast-enhanced ultrasound (CEUS).

PURPOSE: To evaluate neovascularisation within carotid atherosclerotic plaques with contrast enhanced ultrasound. METHODS: We used contrast-enhanced ultrasound to examine 33 patients with carotid atherosclerotic plaques. Plaque size and echogenicity were analyzed and we correlated neovascularization within the plaques. RESULTS: There were 41 atherosclerotic plaques, 27 plaques enhanced after the injection of a contrast agent. Among the group of enhancing plaques we found 8 soft- and 19 mixed plaques. The overall thickness ranging in enhanced plaques was from 1.8 to 4.6 mm. In all cases the contrast uptake in the plaques was later than in the carotid artery. Among the 14 unenhanced atherosclerotic plaques, 4 plaques presented as hard plaques, three calcified plaques, two soft plaques and five presented as mixed plaques. The overall thickness ranging in unenhanced plaques was from 1.7 to 6 mm. CONCLUSION: Contrast-enhanced ultrasound allows the non invasive, dynamic evaluation of neovascularisation within carotid plaques.

Duplex and contrast enhanced ultrasound (CEUS) in evaluation of in-stent restenosis after carotid stenting.

PURPOSE: The aim of the study was to evaluate whether contrast enhanced ultrasound (CEUS) can improve the visualization of in-stent restenosis after carotid stenting of the internal carotid artery (ICA) in comparison to color-coded duplex sonography (CCDS) and power Doppler. MATERIAL AND METHODS: The study included the follow up of thirty patients after carotid artery stenting (CAS). Intrastenotic flow detection and lengths of in-stent restenosis were the main criteria. A high-end ultrasound machine (Siemens, ACUSON, Sequoia or S2000) with a multi-frequency linear 9 MHz or 15 MHz transducer was used to carry out contrast-enhanced ultrasound with SonoVue. In cases of treatment of a high degree in-stent stenosis intra-arterial digital subtraction angiography (DSA) was used. RESULTS: All patients were examined using all diagnostic ultrasound tools of the study. In five patients (17%) an in-stent restenosis of the internal carotid artery (ICA) was found. Two patients need a reintervention. The results show that the contrast enhanced ultrasound could improve the diagnostic assessment capabilities in comparison to CCDS and power Doppler for patients with in-stent restenosis after carotid stenting of the ICA. CONCLUSION: Contrast enhanced ultrasound is a reliable method for the evaluation of in-stent restenosis after carotid stenting of the ICA. CEUS provides a reduction in intrastenotic flow artefacts, resulting in better visualisation and detection of the complete length of the stenosis in comparison with CCDS and power Doppler. In order to elucidate hemodynamic changes, additional Doppler examinations are still necessary.

[Contrast-enhanced sonography for blunt force abdominal trauma]. / Kontrastmittelsonographie beim stumpfen Bauchtrauma.

With the introduction of second generation ultrasound contrast agents, contrast-enhanced ultrasound (CEUS) has become available as an adjunct to the conventional FAST (focused assessment with sonography in trauma) protocol and B-mode sonography of the abdomen after blunt force abdominal trauma. Results from several controlled studies indicate excellent diagnostic accuracy of CEUS for the exclusion of clinically relevant parenchymal injuries after blunt force abdominal trauma. Particularly in younger, hemodynamically stable patients this technique could contribute to a reliable exclusion of parenchymal injuries without the use of ionizing radiation. This report provides details on the technical performance of CEUS, shows examples of typical CEUS findings after blunt abdominal trauma and summarizes the current clinical evidence regarding the use of CEUS after blunt abdominal trauma.

Imaging of carotid arterial diseases with contrast-enhanced ultrasound (CEUS).

Carotid duplex ultrasound is the standard of care for the initial diagnosis of carotid artery bifurcation diseases. But in difficult examinations, carotid abnormalities are commonly encountered and may represent a diagnostic challenge in patients with clinical symptoms as well as in the follow up after carotid endarterectomy or carotid artery stenting. Contrast enhanced ultrasound (CEUS) with low mechanical index (low MI) is a promising new method in the diagnosis and follow up of pathological carotid diseases. Unlike most contrast agents used for magnetic resonance imaging or computed tomography, the microbubbles used in CEUS with SonoVue(®) remain within the vascular space and hence can be used to study vascular disease. In addition to improving current carotid structural scans, CEUS has potential to improve or add extra information on carotid arterial diseases. This review describes the current carotid duplex ultrasound examination and compares the pathological findings with CEUS.

A genetic determinant of the striatal dopamine response to alcohol in men.

Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [(11)C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.

Optimized contrast volume for dynamic CT angiography in renal transplant patients using a multiphase CT protocol.

OBJECTIVES: To study the feasibility of an optimized multiphase renal-CT-angiography (MP-CTA) protocol in patients with history of renal transplantation compared with Doppler-ultrasound (DUS). METHODS: 36 Patients underwent both DUS and time-resolved, MP-CTA (12 phases), with a mean contrast-volume of 34.4±5.1 ml. Quality of MP-CTA was assessed quantitatively (vascular attenuation) and qualitatively (grades 1-4, 1=best). For the assessment of clinical value of MP-CTA, cases were grouped into normal, macrovascular (arterial/venous) and microvascular complications (parenchymal perfusion defect). DUS served as the standard of reference. RESULTS: Using the best of 12 phases in each patient, optimal attenuation was 353±111 HU, 337±98 HU and 164±51 HU in the iliac arteries, renal arteries, and renal veins, respectively. Mean image quality was 1.1±0.3 (n=36) and 2.1±0.6 (n=30) for the transplant renal arteries and veins, respectively. Six renal veins were non-diagnostic in MP-CTA. In 36 patients, MP-CTA showed 13 vascular complications and 10 parenchymal perfusion defects. DUS was not assessable in eight patients. Overall, MP-CTA showed 15 cases with pathology (42%) not identifiable with DUS. The mean effective radiation dose of the MP-CTA protocol was 13.5±5.2 mSv. CONCLUSION: MP-CTA can be sufficiently performed with reduced contrast volume at reasonable radiation dose in renal transplant patients, providing substantially higher diagnostic yield than DUS.

Improving the follow up after EVAR by using ultrasound image fusion of CEUS and MS-CT.

PURPOSE: To evaluate whether the image fusion with contrast enhanced ultrasound (CEUS) and CT affects the diagnosis of endoleaks in unclear cases. METHODS AND MATERIALS: 35 patients with follow-up examinations after endovascular aneurysm repair (EVAR) were included in this retrospective study. Mean patient age was 73 years (range 54-83 y). B-scan, colour doppler and CEUS (1.2 ml SonoVue®, Bracco Imaging Germany) were performed in all patients by an experienced examiner using two different high-end ultrasound system (Siemens ACUSON S2000™, Siemens Healthcare, Erlangen, Germany or Logic E9, GE Healthcare, Milwaukee,WI, USA) with a multifrequency curved array transducer. The examiner was initially blinded to the CT results. Additional image fusion with CT-angiography (CTA) was then performed. The ultrasound examinations were later read by two blinded unbiased investigators with more than five years of clinical ultrasound in consensus. RESULTS: All patients were examined using all diagnostic ultrasound tools of the study. The results show that image fusion is easy and convenient to perform. Conventional ultrasound examination with B-scan and colour Doppler examination detected one Type I and one Type II endoleak, contrast enhanced ultrasound detected one Type I and three Type II endoleaks after EVAR whereas CTA depicted one Type I and two Type II endoleaks. Ultrasound image fusion with CT-angiography confirmed one Type I and three Type II endoleaks. CONCLUSION: In comparison to conventional ultrasound and CTA the use of CEUS improved the visualization and classification of endoleaks. CEUS shows even small blood flow which can be depicted due to the real time imaging of endoleaks. In unclear cases additional ultrasound image fusion with CEUS and CT angiography improves the visualisation of small endoleaks and this may cause a change in the follow-up interval. CEUS is a good alternative to CT in the detection and follow-up of endoleaks, especially in patients with contraindications to CT contrast agents due to allergies or renal failure, enabling reduced additional costs and exposure to radiation.