Edema progression in proximity to traumatic microbleeds: evolution of cytotoxic and vasogenic edema on serial MRI.

Introduction: Although cerebral edema is common following traumatic brain injury (TBI), its formation and progression are poorly understood. This is especially true for the mild TBI population, who rarely undergo magnetic resonance imaging (MRI) studies, which can pick up subtle structural details not visualized on computed tomography, in the first few days after injury. This study aimed to visually classify and quantitatively measure edema progression in relation to traumatic microbleeds (TMBs) in a cohort of primarily mild TBI patients up to 30 days after injury. Researchers hypothesized that hypointense lesions on Apparent Diffusion Coefficient (ADC) detected acutely after injury would evolve into hyperintense Fluid Attenuated Inversion Recover (FLAIR) lesions. Methods: This study analyzed the progression of cerebral edema after acute injury using multimodal MRI to classify TMBs as potential edema-related biomarkers. ADC and FLAIR MRI were utilized for edema classification at three different timepoints: ≤48 hours, ~1 week, and 30 days after injury. Hypointense lesions on ADC (ADC+) suggested the presence of cytotoxic edema while hyperintense lesions on FLAIR (FLAIR+) suggested vasogenic edema. Signal intensity Ratio (SIR) calculations were made using ADC and FLAIR to quantitatively confirm edema progression. Results: Our results indicated the presence of ADC+ lesions ≤48 hours and ~1 week were associated with FLAIR+ lesions at ~1 week and 30 days, respectively, suggesting some progression of cytotoxic edema to vasogenic edema over time. Ten out of 15 FLAIR+ lesions at 30 days (67%) were ADC+ ≤48 hours. However, ADC+ lesions ≤48 hours were not associated with FLAIR+ lesions at 30 days; 10 out of 25 (40%) ADC+ lesions ≤48 hours were FLAIR+ at 30 days, which could indicate that some lesions resolved or were not visualized due to associated atrophy or tissue necrosis. Quantitative analysis confirmed the visual progression of some TMB lesions from ADC+ to FLAIR+. FLAIR SIRs at ~1 week were significantly higher when lesions were ADC+ ≤48 hours (1.22 [1.08-1.32] vs 1.03 [0.97-1.11], p=0.002). Conclusion: Awareness of how cerebral edema can evolve in proximity to TMBs acutely after injury may facilitate identification and monitoring of patients with traumatic cerebrovascular injury and assist in development of novel therapeutic strategies.

Image harmonization improves consistency of intra-rater delineations of MS lesions in heterogeneous MRI.

Clinical magnetic resonance images (MRIs) lack a standard intensity scale due to differences in scanner hardware and the pulse sequences used to acquire the images. When MRIs are used for quantification, as in the evaluation of white matter lesions (WMLs) in multiple sclerosis, this lack of intensity standardization becomes a critical problem affecting both the staging and tracking of the disease and its treatment. This paper presents a study of harmonization on WML segmentation consistency, which is evaluated using an object detection classification scheme that incorporates manual delineations from both the original and harmonized MRIs. A cohort of ten people scanned on two different imaging platforms was studied. An expert rater, blinded to the image source, manually delineated WMLs on images from both scanners before and after harmonization. It was found that there is closer agreement in both global and per-lesion WML volume and spatial distribution after harmonization, demonstrating the importance of image harmonization prior to the creation of manual delineations. These results could lead to better truth models in both the development and evaluation of automated lesion segmentation algorithms.

Virtual Reality Combined with Artificial Intelligence (VR-AI) Reduces Hot Flashes and Improves Psychological Well-Being in Women with Breast and Ovarian Cancer: A Pilot Study.

BACKGROUND AND AIMS: Breast and ovarian cancers affect the lives of many women worldwide. Female cancer survivors often experience hot flashes, a subjective sensation of heat associated with objective signs of cutaneous vasodilatation and a subsequent drop in core temperature. Breast and Ovarian cancer patients also suffer from sleep difficulties and mental health issues. The present study aimed to assess the effectiveness of Bubble, a novel artificial intelligence-virtual reality (AI-VR) intervention for the treatment of hot flashes in female breast or ovarian cancer patients. METHODS: Forty-two women with breast and/or ovarian cancer participated in the study. The mean age was 47 years (range: 25-60 years). Patients suffered from hot flashes at different frequencies. They used Bubble, a virtual reality (VR) mobile psychological intervention based on elements from both cognitive behavioral therapy and mindfulness-based stress reduction. The intervention took place in a VR environment, in a winter wonderland setting called Frosty. Patients were instructed to use Bubble at home twice a day (morning and evening) and when experiencing a hot flash. Participants were asked to use the application for 24 consecutive days. Before and after this 24-day period, patients completed self-report questionnaires assessing hot flashes, general psychiatric distress, perceived stress, illness perception, sleep quality, and quality of life. RESULTS: Between pre- and post-intervention, participants reported a significant reduction in the daily frequency of hot flashes, stress, general psychiatric distress, several domains of QOL, and sleep difficulties, as well as an improvement in illness perception. In addition, they reported very high satisfaction with Bubble. Importantly, both age and baseline levels of psychopathology moderated the effect of Bubble on sleep difficulties. DISCUSSION: This study showed preliminary evidence for the potential of VR interventions in alleviating hot flashes and accompanying mental distress among those coping with breast and ovarian cancer. VR is a powerful therapeutic tool, able to address mind-body aspects in a direct, vivid way. More studies are needed in order to fully understand the potential of this unique intervention.

Cytotoxic Edema Associated with Hemorrhage Predicts Poor Outcome after Traumatic Brain Injury.

Magnetic resonance imaging (MRI) is used rarely in the acute evaluation of traumatic brain injury (TBI) but may identify findings of clinical importance not detected by computed tomography (CT). We aimed to characterize the association of cytotoxic edema and hemorrhage, including traumatic microbleeds, on MRI obtained within hours of acute head trauma and investigated the relationship to clinical outcomes. Patients prospectively enrolled in the Traumatic Head Injury Neuroimaging Classification study (NCT01132937) with evidence of diffusion-related findings or hemorrhage on neuroimaging were included. Blinded interpretation of MRI for diffusion-weighted lesions and hemorrhage was conducted, with subsequent quantification of apparent diffusion coefficient (ADC) values. Of 161 who met criteria, 82 patients had conspicuous hyperintense lesions on diffusion-weighted imaging (DWI) with corresponding regions of hypointense ADC in proximity to hemorrhage. Median time from injury to MRI was 21 (10-30) h. Median ADC values per patient grouped by time from injury to MRI were lowest within 24 h after injury. The ADC values associated with hemorrhagic lesions are lowest early after injury, with an increase in diffusion during the subacute period, suggesting transformation from cytotoxic to vasogenic edema during the subacute post-injury period. Of 118 patients with outcome data, 60 had Glasgow Outcome Scale Extended scores ≤6 at 30/90 days post-injury. Cytotoxic edema on MRI (odds ratio [OR] 2.91 [1.32-6.37], p = 0.008) and TBI severity (OR 2.51 [1.32-4.74], p = 0.005) were independent predictors of outcome. These findings suggest that in patients with TBI who had findings of hemorrhage on CT, patients with DWI/ADC lesions on MRI are more likely to do worse.

Parietal-Prefrontal Feedforward Connectivity in Association With Schizophrenia Genetic Risk and Delusions.

OBJECTIVE: Conceptualizations of delusion formation implicate deficits in feedforward information updating across the posterior to prefrontal cortices, resulting in dysfunctional integration of new information about contexts in working memory and, ultimately, failure to update overfamiliar prior beliefs. The authors used functional MRI and machine learning models to address individual variability in feedforward parietal-prefrontal information updating in patients with schizophrenia. They examined relationships between feedforward connectivity, and delusional thinking and polygenic risk for schizophrenia. METHODS: The authors studied 66 schizophrenia patients and 143 healthy control subjects during performance of context updating in working memory. Dynamic causal models of effective connectivity were focused on regions of the prefrontal and parietal cortex potentially implicated in delusion processes. The effect of polygenic risk for schizophrenia on connectivity was examined in healthy individuals. The authors then leveraged support vector regression models to define optimal normalized target connectivity tailored for each patient and tested the extent to which deviation from this target could predict individual variation in severity of delusions. RESULTS: In schizophrenia patients, updating and manipulating context information was disproportionately less accurate than was working memory maintenance, with an interaction of task accuracy by diagnosis. Patients with delusions also tended to have relatively reduced parietal-prefrontal feedforward effective connectivity during context updating in working memory manipulation. The same connectivity was adversely influenced by polygenic risk for schizophrenia in healthy subjects. Individual patients' deviation from predicted "normal" feedforward connectivity based on the support vector regression models correlated with severity of delusions. CONCLUSIONS: These computationally derived observations support a role for feedforward parietal-prefrontal information processing deficits in delusional psychopathology and in genetic risk for schizophrenia.

Antidepressant-selective gynecomastia.

OBJECTIVE: To describe what we believe is the first reported case of synergistic gynecomastia during treatment of depressive and anxiety disorders when sertraline was added to a stable medication regimen including duloxetine, rosuvastatin, and amlodipine. CASE SUMMARY: A 67-year-old male with major depression, dysthymia, obsessive-compulsive disorder, social anxiety, hypertension, diabetes, and hyperlipidemia presented with new-onset gynecomastia and breast tenderness. Mammography revealed bilateral gynecomastia (fibroglandular tissue posterior to the nipples bilaterally) without suspicious mass, calcification, or other abnormalities. These new symptoms developed after sertraline was added to his stable medication regimen (duloxetine, alprazolam, rosuvastatin, metoprolol, amlodipine, hydrochlorothiazide/triamterene, metformin, and sitagliptin). These symptoms were dose-dependent, with gynecomastia and breast tenderness more severe as sertraline was titrated from 25 mg/day to 50 mg/day and then to 75 mg/day. When sertraline was discontinued, gynecomastia and breast tenderness rapidly resolved. DISCUSSION: Mammoplasia and gynecomastia are associated with altered dopamine neurotransmission and/or perturbations in sexual hormones. These adverse effects may be medication induced. Selective serotonin reuptake inhibitors (sertraline), serotonin-norepinephrine reuptake inhibitors (duloxetine), rosuvastatin, and amlodipine have been reported to cause these adverse effects. This case was unique, since the patient had been on both sertraline and duloxetine previously as independent psychotropics without the development of gynecomastia. In the context of an additive drug adverse effect, the probability of sertraline as the precipitant drug was determined by both the Naranjo probability scale and the Horn drug interaction probability scale as probable. CONCLUSIONS: Gynecomastia is associated with antidepressants and other medications but is rarely addressed. Gynecomastia may be antidepressant selective or may be the result of additive adverse effects. Clinicians are advised to question patients regarding this potential adverse effect. Further education of clinicians is indicated.