Improved Differentiation of Low-Grade and High-Grade Gliomas and Detection of Tumor Proliferation Using APT Contrast Fitted from Z-Spectrum

Purpose

The purpose of the study is to demonstrate the value of quantitative amide proton transfer (APT) imaging for differentiating glioma grades and detecting tumor proliferation.

Procedures

This study included 32 subjects with 16 low-grade gliomas (LGG) and 16 high-grade gliomas (HGG) confirmed by histopathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging with APT weighting was performed on a 3 T scanner. After B₀ correction, Z-spectra were fitted with Lorentzian functions corresponding to the upfield semi-solid magnetization transfer and nuclear overhauser enhancement (MT&NOE) effect, the direct saturation (DS) effect, and the downfield APT effect centered at around ??1.5, 0, and +?3.5 ppm, respectively. To compute the Z-spectral fitted APT (fitted_APT) in solid tumor tissue, double-peak histogram fitting of pixel MT&NOE effect from the whole tumor was used to remove necrosis regions. The fitted APT was then compared with the conventional APT based on magnetization transfer ratio asymmetry. Receiver operating characteristic (ROC) analysis was used to compare the performance between Z-spectral fitted contrasts and the con_APT for LGG versus HGG differentiation. Additionally, the correlations between the imaging contrasts (fitted_APT, con_APT, and fitted_MT&NOE) and Ki-67 labeling index for tumor proliferation were also evaluated.

Results

Z-spectral fitted_APT shows improved statistical power for differentiating HGG and LGG (7.58?±?0.99 vs. 6.79?±?1.05 %, p?<?0.05) than con_APT (4.34?±?0.95 vs. 4.05?±?2.02 %, p?>?0.05) in solid tumor tissues. Analyses of whole tumor, on the other hand, have less differentiating power for both fitted_APT (p from 0.032 to 0.08) and con_APT (p from 0.696 to 0.809). Similarly, based on ROC analyses, fitted_APT shows larger area under the curve (AUC?=?0.723) than con_APT (AUC?=?0.543). The combination of fitted APT, DS, and MT&NOE further improved the specificity (75 %), diagnostic accuracy (78.2 %), and area under the curve (0.758) in differentiating LGG and HGG. Consistently, fitted_APT (r?=?0.451, p?=?0.018) is better correlated with Ki-67 than con_APT (r?=?0.331, p?=?0.092).

Conclusions

Fitted APT from Z-spectrum improves differentiation of low- and high-grade gliomas and better correlated with tumor proliferation than conventional APT.

     

Assessment of Remote Myocardium Heterogeneity in Patients with Ventricular Tachycardia Using Texture Analysis of Late Iodine Enhancement (LIE) Cardiac Computed Tomography (cCT) Images

Purpose

Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease.

Procedures

Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE [energy, entropy, HU-mean, HU-median, standard deviation (SD), and mean absolute deviation (MAD)].

Results

Energy, HU mean, and HU median by cCT texture analysis correlated with ECV (rho?=?0.5650, rho?=?0.5741, rho?=?0.5068; p?<?0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p?<?0.05). SD and MAD correlated with diastolic function by echocardiography (rho?=?0.3837, p?=?0.0071; rho?=?0.3330, p?=?0.0208). MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function.

Conclusions

Texture analysis of LIE may expand cCT capability of myocardial characterization. Myocardial heterogeneity (SD and MAD) was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology.

     

Apparent Diffusion Coefficient is a Useful Biomarker for Monitoring Adipose-Derived Mesenchymal Stem Cell Therapy of Renal Ischemic-Reperfusion Injury

Purpose

This study aimed to investigate the potential of apparent diffusion coefficient (ADC) for monitoring adipose-derived mesenchymal stem cell (ADMSC) therapy of renal ischemic-reperfusion injury (IRI).

Procedures

After baseline magnetic resonance imaging (MRI), 36 Sprague-Dawley rats with bilateral renal IRI were divided equally as groups 1, 2, and 3 (non-treated rats) and groups 4, 5, and 6 (ADMSC-treated rats, with 2 million ADMSCs injected via the tail vein at 6 h after IRI). Groups 1 and 4, 2 and 5, and 3 and 6 were euthanized at days 1, 3, and 7, respectively, after renal MRI. The ratios of ADC at different time points to baseline values in the cortex, outer, and inner stripes of outer medulla (OSOM/ISOM), assessments of monocyte chemoattractant protein-1 (MCP-1), CD68+ cells, tubular cast formation, and degree of fibrosis in three zones over time were compared between the non-treated and ADMSC-treated rats.

Results

Among three zones, the differences in cortical ADC and immunohistochemical changes between the non-treated and ADMSC-treated IRI rats over time were less obvious. Compared with the non-treated rats, the ADMSC-treated rats exhibited significantly higher ADC ratios of OSOM and ISOM at days 1 and 3 corresponding to significantly less MCP-1 staining, CD68+ cells, and tubular casts. From day 3 to day 7, coupling with the decrement of MCP-1 and CD68+ cells in IRI kidneys, the effect of cell density on ADC declined. By day 7, the ADMSC-treated rats showed significantly higher ADC ratios of ISOM than the non-treated IRI rats, indicating better recovery, which could be related to significantly fewer tubular casts and marked amelioration of fibrosis.

Conclusions

We suggest ADC is a useful in vivo biomarker for monitoring ADMSC therapy of renal IRI.

     

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images

Purpose

Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.

Procedures

Data were acquired from three previously reported clinical studies with [⁸⁹Zr]antiCD20 (74 MBq, n?=?7), [⁸⁹Zr]antiEGFR (37 MBq, n?=?7), and [⁸⁹Zr]antiCD44 (37 MBq, n?=?13), with imaging obtained 1 to 6 days post injection (D0–D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq_74inj).Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.

Results

The RC for the combined manually delineated organs for [⁸⁹Zr] antiCD20 (37 MBq_74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq_74inj at D6. For tumor, the RC was up to 42 % for [⁸⁹Zr]antiCD20 (37 MBq_74inj). For [⁸⁹Zr]antiCD20, (18 MBq_74inj), [⁸⁹Zr]antiEGFR (18 MBq_37inj), and [⁸⁹Zr]antiCD44 (18 MBq_37inj), measurement variability was independent of the investigated antibody.

Conclusions

Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.

     

A Transdiagnostic Minority Stress Treatment Approach for Gay and Bisexual Men’s Syndemic Health Conditions

Developing and deploying separate treatments for separate conditions seems ill-suited to intervening upon the co-occurring, and possibly functionally similar, psychosocial conditions facing gay and bisexual men. This article argues for the need to create transdiagnostic interventions that reduce multiple syndemic conditions facing gay and bisexual men at the level of their shared source in minority stress pathways. This article first reviews psychosocial syndemic conditions affecting gay and bisexual men, then suggests pathways that might link minority stress to psychosocial syndemics based on recent advancements in emotion science, psychiatric nosology, and cognitive-affective neuroscience, and finally suggests cross-cutting psychosocial treatment principles to reduce minority stress?syndemic pathways among gay and bisexual men. Because minority stress serves as a common basis of all psychosocial syndemic conditions reviewed here, locating the pathways through which minority stress generates psychosocial syndemics and employing overarching treatment principles capable of simultaneously alleviating these pathways will ultimately create a transdiagnostic approach to improving gay and bisexual men’s health. Clinical research and training approaches are suggested to further validate the pathways suggested here, establish the efficacy of treatment approaches tied to those pathways, and generate effective methods for disseminating a transdiagnostic minority stress treatment approach for gay and bisexual men’s psychosocial syndemic health.     

Assessing the Role of Masculinity in the Transmission of HIV: A Systematic Review to Inform HIV Risk Reduction Counseling Interventions for Men Who Have Sex with Men

HIV affects over 1.2 million people in the United States; a substantial number are men who have sex with men (MSM). Despite an abundance of literature evaluating numerous social/structural and individual risk factors associated with HIV for this population, relatively little is known regarding the individual-level role of masculinity in community-level HIV transmission risk. To address this gap, the current analysis systematically reviewed the masculinity and HIV literature for MSM. The findings of 31 sources were included. Seven themes were identified: (1) number of partners, (2) attitudes toward condoms, (3) drug use, (4) sexual positioning, (5) condom decision-making, (6) attitudes toward testing, and (7) treatment compliance. These factors, representing the enactment of masculine norms, potentiate the spread of HIV. The current article aligns these factors into a masculinity model of community HIV transmission. Opportunities for counseling interventions include identifying how masculinity informs a client’s cognitions, emotions, and behaviors as well as adapting gender-transformative interventions to help create new conceptualizations of masculinity for MSM clients. This approach could reduce community-level HIV incidence.     

Reflections on New York City’s 1947 Smallpox Vaccination Program and Its 1976 Swine Influenza Immunization Program

In 1947, a smallpox outbreak occurred in New York City with a total of twelve cases and two deaths. In order to contain this outbreak, the New York City Department of Health launched a mass immunization campaign that over a period of some 60 days vaccinated 6.35 million people. This article examines in detail the epidemiology of this outbreak and the measures employed to contain it. In 1976, a swine influenza strain was isolated among a few recruits at a US Army training camp at Fort Dix, New Jersey. It was concluded at the time that this virus possibly represented a re-appearance of the 1918 influenza pandemic influenza strain. As a result, a mass national immunization program was launched by the federal government. From its inception, the program encountered a myriad of challenges ranging from doubts that it was even necessary to the development of Guillain-Barré paralysis among some vaccine recipients. This paper examines the planning for and implementation of the swine flu immunization program in New York City. It also compares it to the smallpox vaccination program of 1947. Despite equivalent financial and personnel resources, leadership and organizational skills, the 1976 program only immunized approximately a tenth of the number of New York City residents vaccinated in 1947. The reasons for these marked differences in outcomes are discussed in detail.     

Buffering Syndemic Effects in a Sexual Risk-Reduction Intervention for Male Clients of Female Sex Workers: Results From a Randomized Controlled Trial

Objectives. We sought to test the efficacy of a sexual risk intervention for male clients of female sex workers (FSWs) and examine whether efficacy was moderated by syndemic risk.Methods. From 2010 to 2014, we conducted a 2-arm randomized controlled trial (60-minute, theory-based, safer sex intervention versus a didactic time-equivalent attention control) that included 400 male clients of FSWs on the US–Mexico border with follow-up at 4, 8, and 12 months. We measured 5 syndemic risk factors, including substance use and depression. Primary outcomes were sexually transmitted infections incidence and total unprotected sex with FSWs.Results. Although participants in both groups became safer, there was no significant difference in behavior change between groups. However, baseline syndemic risk moderated intervention efficacy. At baseline, there was a positive association between syndemic risk and unprotected sex. Then at 12 months, longitudinal analyses showed the association depended on intervention participation (B = −0.71; 95% confidence interval [CI] = –1.22, –0.20; P = .007). Among control participants there still existed this modest association (B = 0.36; 95% CI = –0.49, 1.22; P = .09); among intervention participants there was a significant negative association (B = −0.35; 95% CI = –0.63, –0.06; P = .02).Conclusion. A brief intervention might attenuate syndemic risks among clients of FSWs. Other populations experiencing syndemic problems may also benefit from such programs.Male clients of female sex workers (FSWs) represent a “bridge population” that has the potential to transmit HIV and sexually transmitted infections (STIs) between higher-risk groups (FSWs) and lower-risk groups (e.g., their wives).1–3 Globally, male clients of FSWs exhibit high-risk sexual behaviors,4–8 as well as higher STI incidence compared with other men.9 Unfortunately, little intervention work has targeted male clients.In 2007, Lowndes et al. implemented a behavioral intervention focusing on condom promotion among male clients of FSWs in Cotonou, Benin.10 Results suggested that male clients of FSWs in a resource-constrained country can reduce their sexual risk behavior through participation in a targeted behavioral intervention. However, this study lacked randomization and a control condition, precluding the ability to evaluate efficacy to reduce sexual risk behavior. A recent review of randomized trials and quasi-randomized trials of behavioral HIV prevention interventions among sex workers and clients did not identify a single randomized controlled trial targeted for male clients.11In Tijuana, Mexico, a border city along San Diego, California, there are an estimated 6000 to 10 000 FSWs offering sexual services to men from both countries.12 Tijuana has an HIV prevalence that is double the national average, and HIV is highest among high-risk groups including FSWs (approximately 6%).12–14In 2008, we conducted pilot research with 400 male clients of FSWs in Tijuana.13 HIV prevalence among clients was similar to that of FSWs (approximately 5%). Clients reported sex with an FSW an average of 26 times in the past year, once every 2 weeks in the past 4 months, and half reported recent unprotected sex with FSWs. Data were used to develop the first sexual risk-reduction intervention for male clients of FSWs. Herein, we aim to first evaluate the efficacy of our brief intervention, using the rigor of a randomized controlled trial. Whereas evaluating an intervention’s efficacy is a necessary step for HIV prevention, scientists must also examine for whom or under what conditions an intervention is efficacious (i.e., test moderators) to best inform prevention strategies both practically and theoretically.In addition to demonstrating risky sexual behavior, our pilot research with male clients in Tijuana showed that history of drug use was prevalent (88% reporting lifetime drug use) and was associated with unprotected sex with FSWs. These data also showed that the clients were more likely to engage in risky sex if they consumed alcohol at hazardous levels.15 Finally, our qualitative data suggested that vulnerability to HIV was associated with mental health problems like depression or loneliness.16,17 These findings are consistent with previous research on syndemic theory.Research has demonstrated the multiple co-occurrence of psychosocial problems (e.g., substance use, violence) and their additive effect on HIV risk behavior, called “syndemics.”18–21 While the specific factors that are included in the operationalization of a syndemic differ and depend on the specific population and region,21,22 studies have essentially found a dose–response relationship such that individuals who report more psychosocial problems are more likely to engage in higher sexual risk behavior or are more likely to be infected with HIV.23 The second aim of the current research was to examine syndemics as a potential moderator of intervention efficacy. In light of the important role that syndemics play in HIV across high-risk populations, and based on our pilot data, we hypothesized that men who experienced more syndemic problems at baseline would be more likely to benefit from the intervention than men who experienced fewer syndemic problems. Although our sexual risk-reduction intervention was not designed to directly address syndemic problems, it was based on cognitive behavioral therapy, social cognitive theory, and the theory of reasoned action, and we included in the intervention theoretical elements and motivational interviewing techniques designed to promote safer sex behavior by addressing perceived barriers to safer sex.     

Prospective Relation Between Peer Victimization and Suicidal Ideation: Potential Cognitive Mediators

The current study combines models about the effects of peer victimization on negative self-cognitions with models about the effects of negative cognitions on suicidal ideation. In a two-wave longitudinal investigation of high schoolers (N?=?192) and college students (N?=?142), the study examined perceived burdensomeness, thwarted belongingness, and hopelessness as mediators of the prospective relation between peer victimization and suicidal ideation. Path analyses yielded three findings: (a) peer victimization predicted perceived burdensomeness but not thwarted belongingness or hopelessness; (b) perceived burdensomeness, thwarted belongingness, and hopelessness each predicted suicidal ideation; and (c) perceived burdensomeness mediated part of the relation between peer victimization and suicidal ideation. These patterns were consistent across samples and did not differ significantly by gender. Results are consistent with aspects of all three original models and provide support for a new cognitive mediation model regarding the relation of peer victimization to suicidal ideation.