Youth with PHIV have demonstrable subcortical shape deformation related to past HIV severity and cognition; inward deformation was associated with higher peak VL, lower nadir CD4%, and worse cognition. Identifying subcortical deformation may inform clinical practice for early intervention to help improve cognitive outcomes and assess the neuroefficacy of combination antiretroviral therapy in youth with PHIV.

Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age=16.7 years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age=16.1 years). PHIV youth had smaller (2.8 – 5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0 – 13.4%; marijuana use: 10.1 – 16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.

Citation: Leonard J, Flournoy J, Lewis-de los Angeles CP, Whitaker K (2017) How much motion is too much motion? Determining motion thresholds by sample size for reproducibility in developmental resting-state MRI.Research Ideas and Outcomes 3: e12569. https://doi.org/10.3897/rio.3.e12569 AbstractA constant problem developmental neuroimagers face is in-scanner head motion. Children move more than adults and this has led to concerns that developmental changes in restingstate connectivity measures may be artefactual. Furthermore, children are challenging to recruit into studies and therefore researchers have tended to take a permissive stance when setting exclusion criteria on head motion. The literature is not clear regarding our central question: How much motion is too much? Here, we systematically examine the effects of multiple motion exclusion criteria at different sample sizes and age ranges in a large openly available developmental cohort (ABIDE; http://preprocessed-connectomesproject.org/abide). We checked 1) the reliability of resting-state functional magnetic resonance imaging (rs-fMRI) pairwise connectivity measures across the brain and 2) the accuracy with which we can separate participants with autism spectrum disorder from typically developing controls based on their rs-fMRI scans using machine learning. We find that reliability on average is primarily sensitive to the number of participants considered, but that increasingly permissive motion thresholds lower case-control prediction accuracy for all sample sizes. ‡ § | ¶,#

Background: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR = 1.027, p = 0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR = 1.011, p < 0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p = 0.010 t-test), but tumor size was not correlated with female overall survival (p = 0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p = 0.004, F p = 0.001, t-test). Conclusion: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

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; 2 Purpose: Patient sex is recognized as a significant determinant of outcome but the relative prognostic importance of molecular, imaging, and other clinical features of GBM has not yet been thoroughly explored for male versus female patients. Combining multimodal MR images and patient clinical information, this investigation assesses which pretreatment MRIbased and clinical variables impact sexspecific survivorship in glioblastoma patients. Methods:We considered the multimodal MRI and clinical data of 494 patients newly diagnosed with primary glioblastoma (299 males and 195 females). Patient MR images (T1Gd, T2, and T2FLAIR) were segmented to quantify imageable tumor volumes for each MR sequence. Cox proportional hazard (CPH) models and Student's ttests were used to assess which variables were significantly associated with survival outcomes. We used machine learning algorithms to develop pruned decision trees to integrate the impact of these variables on patient survival.

Background: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival. Conclusion: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.