MP2RAGEME: T1, T2*, and QSM mapping in one sequence at 7 tesla

Quantitative magnetic resonance imaging generates images of meaningful physical or chemical variables measured in physical units that allow quantitative comparisons between tissue regions and among subjects scanned at the same or different sites. Here, we show that we can acquire quantitative T₁, T₂^*, and quantitative susceptibility mapping (QSM) information in a single acquisition, using a multi‐echo (ME) extension of the second gradient‐echo image of the MP2RAGE sequence. This combination is called MP2RAGE ME, or MP2RAGEME. The simultaneous acquisition results in large time savings, perfectly coregistered data, and minimal image quality differences compared to separately acquired data. Following a correction for residual transmit B₁⁺‐sensitivity, quantitative T₁, T₂^*, and QSM values were in excellent agreement with those obtained from separately acquired, also B₁⁺‐corrected, MP2RAGE data and ME gradient echo data. The quantitative values from reference regions of interests were also in very good correspondence with literature values. From the MP2RAGEME data, we further derived a multiparametric cortical parcellation, as well as a combined arterial and venous map. In sum, our MP2RAGEME sequence has the benefit in large time savings, perfectly coregistered data and minor image quality differences.     

Directed functional connections underlying spontaneous brain activity

Neuroimaging studies have shown that spontaneous brain activity is characterized as changing networks of coherent activity across multiple brain areas. However, the directionality of functional interactions between the most active regions in our brain at rest remains poorly understood. Here, we examined, at the whole‐brain scale, the main drivers and directionality of interactions that underlie spontaneous human brain activity by applying directed functional connectivity analysis to electroencephalography (EEG) source signals. We found that the main drivers of electrophysiological activity were the posterior cingulate cortex (PCC), the medial temporal lobes (MTL), and the anterior cingulate cortex (ACC). Among those regions, the PCC was the strongest driver and had both the highest integration and segregation importance, followed by the MTL regions. The driving role of the PCC and MTL resulted in an effective directed interaction directed from posterior toward anterior brain regions. Our results strongly suggest that the PCC and MTL structures are the main drivers of electrophysiological spontaneous activity throughout the brain and suggest that EEG‐based directed functional connectivity analysis is a promising tool to better understand the dynamics of spontaneous brain activity in healthy subjects and in various brain disorders.     

A Qualitative Study of Addiction Help-Seeking in People with Different Co-occurring Mental Disorders and Substance Use Problems

People with mental disorders (MD) have high rates of substance use problems (SUP) that are undertreated and understudied despite their adverse outcomes. The objective of this study is to examine barriers and facilitators that influence help-seeking to addiction treatment from the perspective of people with co-occurring MD and SUP. Forty-three individuals with MD and SUP were selected from the sample (n = 127) of a larger research project. This sub-group participated in semi-structured interviews and completed questionnaires. Interview contents were thematically analyzed using a trajectory approach. Based on participants’ addiction trajectories, two mental health experiences were identified: the “multiple disorders experience” and the “anxiety disorder experience.” The analysis highlighted how participants relate to barriers and facilitators to addiction help-seeking at the individual level (denial/minimization of problematic drug use, fear of being labeled an addict, influence of social networks, and knowledge of addiction services) and health system level (waiting time, costs, relationships with health providers, therapeutic approaches, and availability of psychological support). Interventions should be sensitive to the different experiences of people with MD and SUP. Integrated addiction services and a “no wrong door” approach are suggested.     

Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion

Objectives

To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma.

Methods

In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model.

Results

Biliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE (p?<?0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p?<?0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p?<?0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p?<?0.01), and between the dose of chemotherapy and intrahepatic biloma (p?=?0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE (p?=?0.025).

Conclusions

DEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis.

Key points

? DEB-TACE demonstrated more therapy-related hepatic locoregional complications compared to cTACE.? TACE-related hepatic locoregional toxicities occurred more frequently with high baseline PT value.? cTACE may be more appropriate in patients with high baseline PT value.

     

Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia

This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty‐six AD patients, twenty‐one SD patients, and thirty‐nine controls underwent a high‐resolution T1‐MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe — essentially the uncinate and inferior longitudinal fasciculi — in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791–1800, 2017. © 2017 Wiley Periodicals, Inc.     

Intrusions and provoked and spontaneous confabulations on memory tests in Korsakoff’s syndrome

Introduction: Intrusions on verbal memory tests have been used as an index for clinical confabulation. Severe memory impairments in combination with executive dysfunction have been suggested to be the underlying mechanism of confabulation, but to date, this relation is unclear. The aim of this study was (a) to examine the relation between (different types of) intrusions and confabulations in a large sample of confabulating patients with Korsakoff’s syndrome (KS) and (b) to investigate whether different measures of executive functioning and memory performance are related to provoked and spontaneous confabulation. Method: The Dutch version of the California Verbal Learning Test (CVLT) and various executive function and memory tests were administered to a group of 51 confabulating patients with KS. Professional caregivers rated the severity of provoked and spontaneous confabulation behavior of the patients using the Nijmegen–Venray Confabulation List–20 (NVCL–20). Results: The total number of intrusions on the CVLT was not related to either provoked or spontaneous confabulation scores. None of the CVLT intrusion scores correlated significantly with any of the confabulation scores, but we did find small-to-medium, positive correlations between unrelated intrusions and both provoked confabulations and spontaneous confabulation. Provoked confabulation behavior was associated with executive dysfunction and poorer memory performances. Spontaneous confabulation was not related to performance on measures of executive function and memory. Conclusions: The total number of intrusions on verbal memory tests and clinical confabulations appear to be different phenomena. Only unrelated intrusions produced on the CVLT might possibly be related to confabulations. The production of provoked, but not spontaneous, confabulation is associated with executive dysfunction and memory deficits.     

Photodynamic therapy and urothelial carcinoma

PurposePhotodynamic therapy (PDT) is an innovative therapeutic modality in urologic oncology.Material and methodsWe reviewed the current literature on principles and modalities of PDT in urothelial and penile oncology.ResultsPDT has been tested for the treatment recurrent superficial bladder tumors and in situ carcinoma. Carcinologic efficacy has been observed with first generation photosensitizer. The lack of selectivity for tumoral cells was responsible of serious adverse events. Development of selective photosensitizers has reduced the importance of side effects. Data concerning PDT for upper urinary tract urethra and carcinoma are still limited.ConclusionFirst PDT clinical applications in urothelial oncology have shown some effectiveness at the cost of significant morbidity. The development of selective photosensitizers should help to reduce side effects.     

Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways

A subgroup of head and neck squamous cell carcinomas (HNSCCs) contains high‐risk human papillomavirus‐type 16 (HPV16). The viral E6 and E7 oncoproteins inactivate the p53 and pRb proteins, respectively. We examined the causative effect of HPV16 E6 and E7 expression on the immortalization of normal oral keratinocytes (OKCs) and compared the resulting phenotype with alternative ways of p53‐ and pRb‐pathway abrogation frequently found in HNSCCs without HPV. Primary OKCs were conditionally immortalized with temperature‐sensitive SV40 large T‐antigen and human telomerase, allowing these cells to return to their senescent primary state after temperature shift. HPV16 E6 and E7 were introduced to overcome senescence, determined with population doubling (PD) as read‐out. For comparison, we downregulated p53 and p16 by short hairpin RNA genes and expressed mutant p53R(175)H and cyclinD1. Expression of HPV16 E6 caused an extended life span similar to expression of mutant p53R(175)H or p53 knockdown. Expression of mutant p53R(175)H seemed to cause additional activation of the hypoxia and WNT signaling pathways. HPV16 E7 expression had no direct effect on lifespan, similar to p16 knockdown or cyclinD1 expression. In combination with HPV16 E6 or other functional inactivations of p53, abrogation of the pRb‐pathway by either HPV16 E7 or other manipulations caused an immortal phenotype. Our data show the causative role of HPV16 E6/E7 in early squamous carcinogenesis. Activity of each gene could be mimicked by other genetic events frequently found in HNSCC without HPV. This data provides the experimental proof of causal association of HPV in HNSCC carcinogenesis and further support the crucial role of the p53‐ and pRb‐pathways.