Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity.

BACKGROUND: The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders. METHOD: A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998-2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA. RESULTS: The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives. CONCLUSIONS: The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.

The relationship between cannabis involvement and suicidal thoughts and behaviors.

BACKGROUND: In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology. METHODS: We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI. RESULTS: All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs]=1.28-2.00, p<0.01). Cannabis use and endorsing ≥3 symptoms were associated with unplanned (SANP; ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts (p>0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG=0.45) and environmental (rE=0.21) factors were responsible for the covariance between cannabis involvement and SI. CONCLUSIONS: Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders.

[MR-guided coil embolisation of renal arteries in an animal model]. / MR-gesteuerte Spiralembolisation von Nierenarterien in einem Tiermodell.

PURPOSE: To test the feasibility of MR-guided coil embolization with passive visualization in an animal model. MATERIALS AND METHODS: All experiments were performed on a 1.5 T interventional MR-scanner (Gyroscan ACS-NT, Philips, Netherlands). A gradient echo sequence was combined with radial k-space acquisition and sliding window reconstruction technique to calculate the raw data with a specially designed back projector, yielding a frame rate of 20 images per second. The images were directly displayed on LCD-screens next to the MR scanner. A multipurpose catheter with dysprosium markers was placed into the renal arteries of two pigs under MR guidance, and a nitinol coil and platinum coil each were deployed. The position of the coils was verified with magnetic resonance angiography and conventional angiography. RESULTS: MR-guided catheterization of renal arteries with subsequent coil embolization was successfully carried out but the configuration of the coils could not be visualized on the MR images. CONCLUSION: MR-guided coil embolization of renal arteries is feasible. Exact guidance of coil deployment is not attainable with passive visualization.

A twin study of genetic and environmental influences on suicidality in men.

BACKGROUND: Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders. METHODS: Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors. RESULTS: The prevalence of suicidal ideation and suicide attempt were 16.1% and 2.4% respectively. In a multinomial regression model, co-twin's suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin's suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects. CONCLUSIONS: There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.

Suicide attempts in an adolescent female twin sample.

OBJECTIVE: To examine suicide attempts in an epidemiologically and genetically informative youth sample. METHOD: 3,416 Missouri female adolescent twins (85% participation rate) were interviewed from 1995 to 2000 with a telephone version of the Child Semi-Structured Assessment for the Genetics of Alcoholism, which includes a detailed suicidal behavior section. Mean age was 15.5 years at assessment. RESULTS: At least one suicide attempt was reported by 4.2% of the subjects. First suicide attempts were all made before age 18 (and at a mean age of 13.6). Major depressive disorder, alcohol dependence, childhood physical abuse, social phobia, conduct disorder, and African-American ethnicity were the factors most associated with a suicide attempt history. Suicide attempt liability was familial, with genetic and shared environmental influences together accounting for 35% to 75% of the variance in risk. The twin/cotwin suicide attempt odds ratio was 5.6 (95% confidence interval [CI] 1.75-17.8) for monozygotic twins and 4.0 (95% CI 1.1 -14.7) for dizygotic twins after controlling for other psychiatric risk factors. CONCLUSIONS: In women, the predisposition to attempt suicide seems usually to manifest itself first during adolescence. The data show that youth suicide attempts are familial and possibly influenced by genetic factors, even when controlling for other psychopathology.

Comparison of aerosolized gadoteridol and gadopentetate dimeglumine for magnetic resonance ventilation imaging of the lung.

The purpose of this study was to compare aerosolized gadoteridol and gadopentetate dimeglumine in regard to homogeneity of aerosol distribution and relative pulmonary signal intensity (SI) changes after a 10-min mechanical ventilation period. Twenty experimental procedures were performed in 10 intubated domestic pigs that were mechanically aerosolized with the nebulized contrast medium. Images were obtained by using a respiratory-gated T(1)-weighted TSE sequence. Pulmonary SI increase for the right and left lung was 26% +/- 25% and 25% +/- 12%, respectively, for gadopentetate dimeglumine, and 45% +/- 12% and 43% +/- 10%, respectively, for gadoteridol. Aerosol distribution was rated homogeneous in all cases by two readers. It is concluded that both contrast agents in aerosolized form are capable of depicting pulmonary ventilation in healthy animals with lung capacities comparable to those of humans. SI differences between gadoteridol and gadopentetate dimeglumine are explained by their considerable difference in viscosity.

Real-time MR Guidance for inferior vena cava filter placement in an animal model.

It was the aim of this study to examine the feasibility of real-time magnetic resonance (MR) imaging for MR-guided placement of inferior vena cava (IVC) filters, which were placed in five pigs via a femoral approach. The introducer sheath and dilator were marked with Dysprosium rings. The procedures were performed under MR guidance with use of a 1.5-T ACS-NT imager. Radial filling of k-space in conjunction with the sliding window reconstruction technique achieved real-time MR imaging with a frame rate of 20 images/sec. Simultaneous real-time visualization of the vascular anatomy and interventional instruments was achieved under real-time conditions and allowed correct placement of IVC filters in all five cases as confirmed by radiographic angiography.

MR-guided percutaneous drainage of abdominal fluid collections in combination with X-ray fluoroscopy: initial clinical experience.

The aim of this study was to examine the feasibility of a hybrid interventional MR system, which combines a closed bore magnet with a C-arm fluoroscopy unit for percutaneous drainage of abdominal fluid collections. During the past 2 years, we have performed four drainage procedures in four patients (mean age 47 years). Three patients had abscesses (psoas muscle, kidney, subphrenic location) and the fourth patient had a recurrent splenic cyst. All procedures were performed on an interventional MR system consisting of a 1.5-T ACS-NT scanner combined with a specially shielded C-arm. The drainages were guided by T1-weighted fast gradient-echo images, T2-weighted single-shot turbo spin-echo images or both. A standard 18 G (1.2 mm) nonferromagnetic stainless steel needle with a Teflon sheath was used for the punctures following which a 0.89 mm nitinol guidewire was inserted into the fluid collection. Thereafter, the patient was positioned in the immediate adjacent fluoroscopy unit and a drainage catheter was placed under fluoroscopic control. All drainage catheters were successfully placed into the fluid collections, as proven by fluid aspiration and resolution of the collection. The mean time needed for the entire drainage procedure (MR and fluoroscopy) was 110 min. No procedure-related complications occurred. It is feasible to perform drainage procedures on a closed-bore MR scanner. The multiplanar imaging capabilities of MR are particularly helpful for fluid collections in the subphrenic location.

Mechanical delivery of aerosolized gadolinium-DTPA for pulmonary ventilation assessment in MR imaging.

RATIONALE AND OBJECTIVES: To evaluate a new technique with mechanical administration of aerosolized gadolinium (Gd)-DTPA for MR visualization of lung ventilation. METHODS: Ten experimental procedures were performed in six domestic pigs. Gd-DTPA was aerosolized by a small-particle generator. The intubated animals were mechanically aerosolized with the nebulized contrast agent and studied on a 1.5-T MR imager. Respiratory gated T1-weighted turbo spin-echo images were obtained before, during, and after contrast administration. Pulmonary signal intensity (SI) changes were calculated for corresponding regions of both lungs. Homogeneity of aerosol distribution was graded independently by two radiologists. RESULTS: To achieve a comparable SI increase as attained in previous trials that used manual aerosol ventilation, a ventilation period of 20 minutes (formerly 30 minutes) was sufficient. Mean SI changes of 116% were observed after that duration. Contrast delivery was rated evenly distributed in all cases by the reviewers. CONCLUSIONS: The feasibility of applying Gd-DTPA as a contrast agent to demonstrate pulmonary ventilation in large animals has been described before. The results of this refined technique substantiate the potential of Gd-based ventilation MR imaging by improving aerosol distribution and shortening the nebulization duration in the healthy lung.

Experimental MR imaging-guided interstitial cryotherapy of the brain.

BACKGROUND AND PURPOSE: Hyperthermal ablation techniques such as laser or RF ablation require dedicated heat-sensitive MR imaging sequences for monitoring MR imaging--guided interventions. Because cryotherapy does not have these limitations, the purpose of this study was to evaluate the feasibility of MR imaging--guided percutaneous cryotherapy of the brain. METHODS: An experimental cryoprobe with an outer diameter of 2.7 mm was inserted into the right frontal lobe of 11 healthy pigs under MR imaging control. Freezing procedures were monitored by using an interventional 1.5-T magnet and a gradient-echo sequence with radial k-space trajectories, a fast T2-weighted single-shot spin-echo sequence, and a T1-weighted single-shot gradient-echo sequence. In three animals, the procedure was also monitored by using dynamic CT. A freeze-thaw cycle with a duration of 3 minutes was repeated three times per animal. Follow-up MR images were obtained 3, 7, and 14 days after cryotherapy by using conventional MR sequences. Six animals were killed 7 days after intervention, and five animals were killed 14 days after intervention. The brains were sectioned, and the histologic findings of the lesions were compared with the MR imaging appearance. RESULTS: No artifacts due to the probe were observed on the MR images or CT scans. The ice formation (mean diameter, 12.5 mm) was very well delineated as a signal-free sphere. MR monitoring of the freezing procedure yielded a significantly higher ice:tissue contrast than did CT. The size of the ice ball as imaged by MR imaging and CT during the intervention correlated well with the MR imaging appearance of the lesions at the 14-day follow-up examination and with the histologic findings. Histologically, coagulation necrosis and gliosis were found, surrounded by a transition zone of edema and a disrupted blood-brain barrier, corresponding to a contrast-enhancing rim around the lesions on follow-up MR images. CONCLUSION: MR imaging-guided cryotherapy of the brain is possible and allows a precise prediction of the resulting necrosis. MR imaging of the freezing process does not require heat-sensitive sequences and is superior to CT for monitoring of cryoablation.

Real-time MR fluoroscopy for MR-guided iliac artery stent placement.

The purpose of this study was to test the feasibility of real-time magnetic resonance (MR) guidance of iliac artery stent placement. Radial scanning together with the sliding window reconstruction technique was implemented on a 1.5 T magnet, yielding a frame rate of 20 images per second. Seven prototype nitinol ZA stents were deployed in iliac arteries of living pigs under MR control. All stents were well visualized on the radial MR images, allowing depiction of the mounted stents as well as stent deployment without anatomy-obscuring artifacts. Stent placement was sucessful in all cases and took 6 minutes on average. The position of the stents was correctly visualized by real-time radial MR scanning, as proved by digital subtraction X-ray angiography. Combined radial scanning and the sliding window reconstruction technique allow real-time MR-guided stent placement in iliac arteries.

Social phobia in a population-based female adolescent twin sample: co-morbidity and associated suicide-related symptoms.

BACKGROUND: This report attempted to replicate and extend prior work examining social phobia (SP), co-morbid psychiatric illnesses, and the risk of suicidal ideation and suicide attempts incurred by their adolescent sufferers. METHODS: SP, alcohol dependence (ALD) and major depressive disorder (MDD) diagnoses, and suicide-related symptoms, were assessed in a population-based adolescent female twin sample. The differentiation of risks as a function of co-morbidity was explored. A trivariate model was fitted to estimate sharing of genetic and environmental vulnerability between SP and co-morbid disorders. RESULTS: The lifetime prevalence of SP was 16.3 %. Significant risk for co-morbid MDD (OR = 3.2) and ALD (OR = 2.1) was observed. Strong evidence for shared genetic vulnerability between SP and MDD (respective heritabilities 28%, 45%; genetic r = 1.0) was observed with moderate support noted for similar sharing between SP and ALD (genetic r = 0.52, heritability for ALD 63%). SP with co-morbid MDD was associated with elevated risk for ALD and for suicide-related symptoms. CONCLUSIONS: SP is a common illness often followed by co-morbid MDD and ALD. SP with comorbid MDD predicts a substantially elevated risk of ALD and suicide-related symptoms, stressing the need for early SP detection.

[Aerosolized gadolinium-DTPA for demonstration of pulmonary ventilation in magnetic resonance tomography]. / Aerosoliertes Gadolinium-DTPA zur Darstellung der Lungenventilation in der Magnetresonanztomographie.

PURPOSE: Magnetic resonance assessment of lung ventilation with aerosolized Gd-DTPA. METHODS: Eleven experimental procedures were carried out in a domestic pig model. The intubated pigs were aerosolized for 30 minutes with an aqueous formulation of Gd-DTPA. The contrast agent aerosol was generated by a small particle aerosol generator. Imaging was performed on a 1.5 T MR imager using a T1-weighted turbo spin echo sequence with respiratory gating (TR 141 ms, TE 8.5 ms, 6 averages, slice thickness 10 mm). Pulmonary signal intensities before and after ventilation were measured in peripheral portions of both lungs. RESULTS: Immediately after ventilation with aerosolized Gd-DTPA, the signal intensity in both lungs increased significantly in all animals with values up to 237% above baseline (mean 139% +/- 48%), but with in some cases considerable regional intra- and interindividual intensity differences. Distinctive parenchymal enhancement was readily visualized in all eleven cases with good spatial resolution. CONCLUSION: The presented data indicate that Gd-DTPA in aerosolized form can be used to demonstrate pulmonary ventilation in large animals with lung volumes comparable to man. Further experimental trials are necessary to improve reproducibility and to define the scope of this method for depicting lung disease.

MRI of the inner ear: comparison of axial T2-weighted, three-dimensional turbo spin-echo images, maximum-intensity projections, and volume rendering.

RATIONALE AND OBJECTIVES: To compare the ability of axial T2-weighted, three-dimensional, turbo spin-echo (3D TSE) images, targeted maximum-intensity projections (MIPs), and 3D volume reconstructions to depict anatomic details of the labyrinth. METHODS: In 24 volunteers, 3D TSE images were obtained. MIPs and 3D volume reconstructions were performed from the acquired data. All images were evaluated by three radiologists independently regarding the visualization of the different anatomic structures. RESULTS: In the axial slices, most anatomic details were visible in comparison with observations by the other modalities. The 2.5 windings of the cochlea were best depicted on the MIPs. Volume reconstructions rendered excellent spatial information regarding the vestibule and semicircular canals and were the only technique that demonstrated all three ampullae in all cases. CONCLUSIONS: Axial TSE images, MIPs, and 3D volume reconstructions are complementary modalities that provide different information. Our results suggest that improved diagnostic information can be obtained by applying these volume visualization reconstruction techniques.

[Radial k-scanning for real-time MR imaging of central and peripheral pulmonary vasculature]. / Radiale k-Raumabtastung zur MR-tomographischen Echtzeitdarstellung der zentralen und peripheren Pulmonalgefässe.

PURPOSE: To depict the central and peripheral pulmonary vessel anatomy with real-time radial MR scanning without respiratory control. METHODS: Three healthy volunteers and one patient with pulmonary embolism proven by spiral CT angiography were studied with a 1.5 T MR imaging system. First, a breath-hold, contrast-enhanced MR angiography was performed for comparison of accuracy. Gradient echo images (TR 16 ms, TE 4 ms, flip angle 18 degrees) were obtained applying a combination of radial scanning and the sliding window reconstruction technique. A dedicated back-projector allowed data reconstruction in real-time with a frame rate of 20 images per second. Scanning was performed during free breathing. RESULTS: The described technique depicted the central and peripheral portions of the normal pulmonary anatomy with comparable image quality as the 3D contrast-enhanced angiography. Visualization of the pulmonary emboli as demonstrated by spiral CT was possible. CONCLUSION: Real-time radial scanning allows promising image acquisition of the pulmonary vasculature without respiratory control. Further technical improvements and clinical trials are required to evaluate its role in the diagnosis of vascular pathologies.

[Interventional magnetic resonance imaging--non-invasive imaging for interventions]. / Interventionelle Magnetresonanz-tomographie--nichtinvasive Bildgebung für Interventionen.

As a prerequisite for MR-guidance of interventional procedures, instruments have to be well depicted in the MR image without obscuring or distorting the underlying anatomy. For non-vascular interventions the imaging speed has to be in the range of seconds while control of vascular interventions requires real time imaging speed. The imaging contrast has to be maintained as well as a high spatial resolution. Furthermore, sufficient patient access has to be provided by the MR scanner. Neither an ideal magnet nor the optimal single sequence are available to fulfill the above-mentioned criteria. The type of sequence--gradient echo versus spin echo--together with changing of the echo time and phase encoding direction will ensure an appropriate size of the artifact and thereby of the appearance of the instrument in the MR image. The feasibility of non-vascular MR-guided interventions has been proved at field strengths ranging from 0.064 T to 1.5 T. Bone biopsies, soft tissue biopsies, drainages, and control of interstitial thermo- and cryotherapy have been reported. For vascular interventions, different real time MR strategies are currently under investigation. The development of dedicated catheters and guide wires has enabled MR-guided dilatations, stenting, placement of vena cava filters, and TIPS procedures. Considering the fast progress being made in this field, there can be no question that interventional MRI will become a well-accepted clinical tool offering potential advantages such as excellent soft tissue contrast, multiplanar imaging, flow measurements, high resolution imaging of vessel walls, and lack of ionizing radiation.

A perspective on needle artifacts in MRI: an electromagnetic model for experimentally separating susceptibility effects.

A thorough understanding of artifacts caused by metallic instruments is essential for the guidance of interventional procedures by magnetic resonance imaging (MRI), because the accurate localization of each instrument is mandatory for this. In the past, this problem has been addressed by several groups, using theoretical, as well as experimental approaches. The artifacts associated with MRI are caused by geometry distortion and intravoxel dephasing. Usually, both effects mingle in the image, and depending on the pulse sequences and its parameters used for data acquisition, these effects are reflected in the image with different magnitude. In this paper we shortly present the well-known mathematical background of the two underlying effects. Mathematically, both can be treated separately. Here, we propose a new electromagnetic model which also allows to experimentally separate the effects better than by comparing spin-echo and gradient-echo images of the same object. With this new model, both effects-geometry distortion and intravoxel dephasing-are demonstrated separately using the same gradient-echo pulse sequence for all scans and adjusting the fields of the model properly. Furthermore, as this model allows to adjust both effects independently, it is used to study different weightings of both effects when they appear simultaneously in the image.

MR imaging-guided percutaneous nephrostomy and use of MR-compatible catheters in the nondilated porcine urinary tract.

PURPOSE: To investigate technique and practicability of MR-guided percutaneous nephrostomy (MRPCN) and to test magnetic resonance (MR)-compatible catheters inside the urinary tract. MATERIALS AND METHODS: In 10 healthy pigs, a percutaneous nephrostomy tube was placed into the nonobstructed pelvicaliceal system with use of exclusive MR guidance with a standard 1.5-T magnet. The urinary tract was visualized by intravenous injection of Gd-DTPA in combination with low-dose furosemide. The procedure was controlled with use of a T1-weighted turbo gradient-echo sequence in two orthogonal planes. The equipment for MRPCN included an 18-gauge MR-compatible puncture needle, a nitinol guide wire, and different 5-F MR catheters. RESULTS: In all 10 animals, the puncture needle was safely directed into the nondilated target calix. Slight deviations of the needle were detected on both MR image planes, which enabled immediate correction. This technique achieved a "first attempt" puncture of the targeted calix in each animal. MR images accurately demonstrated the dysprosium labelled tip of the different inserted catheters. It proved essential to inject a gadolinium-insaline solution via these catheters to preserve the endoluminal contrast enhancement as long as necessary. Balloon catheters were directed and inflated inside the ureter under exclusive MR guidance. Complications such as perforation and leakage were visualized by MR imaging. CONCLUSIONS: MRPCN is a promising technique for puncturing the pelvicaliceal system. The ability to successfully enter the urinary tract, even when it is nondilated, underscores the accuracy achievable with multiplanar MR imaging.

[MR defecography at 1.5 Tesla with radial real-time imaging and reduced image field]. / MR-Defäkographie bei 1,5 Tesla mit radialer Echtzeitbildgebung und reduziertem Bildfeld.

PURPOSE: To evaluate a new technique for MR defecography with real-time imaging using radial k-space profiles. MATERIALS AND METHODS: A catheter-mounted condom was inserted into the rectum of 16 patients and filled in situ by a mixture of Nestargel and Gadolinium. After multiplanar imaging of the pelvis by high resolution T2-weighted turbo-spin echo sequences, defecation was imaged by a gradient echo sequence with radial k-space filling using a reduced field of view (rFOV) in real-time. The documentation was performed on an S-VHS recorder. RESULTS: At a constant background signal, radial k-space filling yields a real-time impression. An interactive software allowed the operator to modify the slice thickness, slice plane, flip angle and slice angulation during scanning, resulting in an optimum imaging quality of the defecation. CONCLUSIONS: This new imaging technique allows real-time MR defecography in a high-field scanner and provides all anatomical und functional information of the defecation.