Automatic segmentation of the brain and intracranial cerebrospinal fluid in T1-weighted volume MRI scans of the head, and its application to serial cerebral and intracranial volumetry.

A new fully automatic algorithm for the segmentation of the brain and total intracranial cerebrospinal fluid (CSF) from T(1)-weighted volume MRI scans of the head, called Exbrain v.2, is described. The algorithm was developed in the context of serial intracranial volumetry. A brain mask obtained using a previous version of the algorithm forms the basis of the CSF segmentation. Improved brain segmentation is then obtained by iterative tracking of the brain-CSF interface. Gray matter (GM), white matter (WM), and intracranial CSF volumes and probability maps are calculated based on a model of intensity probability distribution (IPD) that includes two partial volume classes: GM-CSF and GM-WM. Accuracy was assessed using the Montreal Neurological Institute's (MNI) digital phantom scan. Reproducibility was assessed using scan pairs from 24 controls and 10 patients with epilepsy. Segmentation overlap with the gold standard was 98% for the brain and 95%, 96%, and 97% for the GM, WM, and total intracranial contents, respectively; CSF overlap was 86%. In the controls, the Bland and Altman coefficient of reliability (CR) was 35.2 cm(3) for the total brain volume (TBV) and 29.0 cm(3) for the intracranial volume (ICV). Scan-matching reduced CR to 25.2 cm(3) and 17.1 cm(3) for the TBV and ICV, respectively. For the patients, similar CR values were obtained for the ICV.     

Detection of renal masses: sensitivities and specificities of excretory urography/linear tomography, US, and CT

A prospective blinded study of 201 patients was performed to determine the relative sensitivities and specificities of excretory urography/linear tomography (EU/LT) and ultrasound (US) for the diagnosis of renal parenchymal masses. Computed tomography (CT) was used as a standard. EU/LT permitted detection of 10% of CT-confirmed masses (cystic or solid) less than 1 cm, 21% of lesions greater than or equal to 1 cm but less than 2 cm, 52% of lesions greater than or equal to 2 cm but less than 3 cm, and 85% of lesions 3 cm or more in diameter. US permitted detection of 26% of CT-confirmed lesions less than 1 cm, 60% of lesions greater than or equal to 1 cm but less than 2 cm, 82% of lesions greater than or equal to 2 cm but less than 3 cm, and 85% of lesions 3 cm or more in size. The results confirm the relative insensitivity of EU/LT for masses less than 3 cm in diameter and of US for masses less than 2 cm. Further, they suggest that CT may have a role not only in evaluation of cases in which the urographic or sonographic results are questionable or positive, but also in confirmation of apparently negative urographic findings when clinical suspicion of a lesion is high.     

Active Smoking May Negatively Affect Response Rate,Progression‐Free Survival,and Overall Survival of Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib

Background.

Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC).

Methods.

An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors.

Results.

Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p < .0001), non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p < .0001), use of angiotensin system inhibitors (HR: 0.63, p = .01), sunitinib dose reduction or treatment interruption (HR: 0.72, p = .045), and Heng risk (good and intermediate risk: HR: 1.07, p = .77; poor risk: HR: 1.87, p = .046). Factors associated with OS were smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p < .0001), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 2.95, p < .0001), and sunitinib-induced hypertension (HR: 0.57, p = .002).

Conclusion.

Active smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.     

Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: An [C]diprenorphine PET study

The importance of the opioid receptor system in substance dependence is increasingly recognised. We used PET with the non-selective tracer [¹¹C]diprenorphine to examine opioid receptor binding in early abstinence from alcohol dependence and the relationship to craving. We recruited 11 alcohol dependent patients and 13 controls. Subjects underwent one [¹¹C]diprenorphine PET scan in early abstinence from dependent alcohol use ( 2 weeks) and 2 months later if continuously abstinent. Global and regional [¹¹C]diprenorphine volumes of distribution (VD) were increased in alcohol dependent patients compared with controls but did not reach significance. We demonstrated a correlation between global and regional [¹¹C]diprenorphine VD and craving in alcohol dependent patients which persisted in the anterior cingulate cortex into extended abstinence. This confirms previous work showing increased opioid receptor availability in early abstinence from substances of abuse and correlation with craving suggesting that the opioid system plays a fundamental role in this phase of addiction.     

PET measurement of the influence of corticosteroids on serotonin-1A receptor number.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis and serotonergic system interact functionally. The modulatory effect of corticosteroids on 5-HT(1A) receptor number and function has been repeatedly demonstrated in preclinical studies suggesting that raised corticosteroid levels decrease 5-HT(1A) receptor number and function in the hippocampus. METHODS: We used positron emission tomography (PET) to quantify the number of 5-HT(1A) receptors in two studies, the first in normal subjects given a single dose of hydrocortisone using a random-order, double-blind, placebo-controlled design and second in patients treated long-term with corticosteroids. RESULTS: We did not find that exposure to elevated levels of corticosteroids in either the short or long term alters 5-HT(1A) receptor binding in the hippocampus or other brain regions examined. CONCLUSIONS: This study does not support the hypothesis that corticosteroids exert a major inhibitory regulatory control over the 5-HT(1A) receptor binding in the human brain.     

The relationship of malingering test failure to self-reported symptoms and neuropsychological findings in adults referred for ADHD evaluation

Diagnosis of adult attention-deficit/hyperactivity disorder (ADHD) adults is difficult, as neither symptom report nor neuropsychological findings are specific to ADHD. Few studies address the possibility that noncredible performance influences both symptom report and neuropsychological findings. The present study utilized archival data from young adults referred for concerns about ADHD, divided into three groups: (1) those who failed a measure of noncredible performance (the Word Memory Test; WMT), (2) those who met diagnostic criteria for ADHD, and (3) controls with psychological symptoms but no ADHD. Results showed a 31% failure rate on the WMT. Those who failed the WMT showed clinical levels of self-reported ADHD symptoms and impaired neuropsychological performance. Neither self-report measures nor neuropsychological tests could distinguish ADHD from psychological controls, with the exception of self-reported current hyperactive/impulsive symptoms and Stroop interference. Results underscore the effect of noncredible performance on both self-report and cognitive measures in ADHD.