A different interpretation of the DIANA fMRI signal.

Direct detection of neural activity by functional magnetic resonance imaging (fMRI) has been a longstanding goal in neuroscience. A recent study argued that it is possible to detect neuroelectrical potentials using a specialized fMRI scanning approach the authors termed "direct imaging of neuronal activity" (DIANA). We implemented DIANA in anesthetized rats and measured responses to somatosensory stimulation, reproducing core findings of the original study. We show, however, that neural activity is neither sufficient nor necessary to produce such results. We use a combination of control conditions and simulations to demonstrate that DIANA signals can arise from nonideal aspects of the pulse sequence and specimen that help determine spatiotemporal characteristics of the data. Our analysis emphasizes a need for cautious interpretation and mechanistic evaluation of advanced fMRI techniques.

Imaging bioluminescence by detecting localized haemodynamic contrast from photosensitized vasculature.

Bioluminescent probes are widely used to monitor biomedically relevant processes and cellular targets in living animals. However, the absorption and scattering of visible light by tissue drastically limit the depth and resolution of the detection of luminescence. Here we show that bioluminescent sources can be detected with magnetic resonance imaging by leveraging the light-mediated activation of vascular cells expressing a photosensitive bacterial enzyme that causes the conversion of bioluminescent emission into local changes in haemodynamic contrast. In the brains of rats with photosensitized vasculature, we used magnetic resonance imaging to volumetrically map bioluminescent xenografts and cell populations virally transduced to express luciferase. Detecting bioluminescence-induced haemodynamic signals from photosensitized vasculature will extend the applications of bioluminescent probes.

Fiber-based Probes for Electrophysiology, Photometry, Optical and Electrical Stimulation, Drug Delivery, and Fast-Scan Cyclic Voltammetry In Vivo.

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and imaging of fluorescent indicators. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by simultaneously interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.

Prospective evaluation of radiographic manifestations of tuberculosis in relationship with CD4 count in patients with HIV/AIDS.

A major risk factor to develop active tuberculosis (TB) is the infection with the human immunodeficiency virus (HIV). Chest radiography is the first-line imaging modality used to rule out TB. Coinfected individuals present often with atypical imaging patterns, due to the immunosuppression caused by the virus, making diagnosis difficult. In this prospective observational study 268 TB and HIV coinfected patients were included. During a follow-up period of 24 weeks, the predominant patterns on chest radiography were analyzed and compared to the cluster of differentiation 4 (CD4) count under antiretroviral and anti-TB therapy. Patients with low CD4 counts (<200 cells//µL) showed more often lymphadenopathy (62% vs 38%;P = .08) and a miliary pattern (64% vs 36%;P = .04) but less likely cavitation (32% vs 68%;P = .008) or consolidation (47% vs 63%;P = .002) compared to individuals with higher CD4 counts. Over the follow-up period, partial response to therapy was the most frequent radiological evolution (62%), mainly accompanied by an increase of CD4 cells (92%). Patients with a decrease in CD4 count mostly presented with a worsening in radiological findings (53%). Radiographic TB manifestation correlated with the immune status of patients coinfected with HIV. Low CD4 counts often showed atypical manifestation.

Intravoxel Incoherent Motion Analysis of Abdominal Organs: Application of Simultaneous Multislice Acquisition.

PURPOSE: The aim of this study was to systematically evaluate the accuracy of quantitative intravoxel incoherent motion (IVIM) analysis of the upper abdomen applying simultaneous multislice (SMS) diffusion-weighted imaging (DWI) to reduce acquisition time. MATERIALS AND METHODS: Diffusion-weighted imaging of parenchymal abdominal organs was performed in 8 healthy volunteers at 3 T using a standard DWI sequence (acceleration factor 1 [AF1]) and an SMS-accelerated echo planar imaging sequence with acceleration factors 2 and 3 (AF2/AF3). Intravoxel incoherent motion analysis was performed with a multistep algorithm for true diffusion coefficient (Dt), pseudodiffusion coefficient (D*), and fraction of perfusion (Fp) measured for the liver, kidney cortex and medulla, pancreas, spleen, and erector spinae muscle. Qualitative and quantitative parameters were compared using a repeated measurement 1-way analysis of variance test and the Bonferroni post hoc method. RESULTS: Simultaneous multislice DWI provided diagnostic image quality in all volunteers with a reduction of scan time of 50% for AF2 (67% for AF3) compared with the standard sequence. Decent IVIM analysis for Dt, D*, and Fp can be calculated on the images of both the SMS sequences AF2 and AF3 with typical organ characteristics of IVIM; however, systematical deviations from AF1 were observed: Dt values increased and Fp decreased significantly with higher acceleration factor for liver, kidney, pancreas, and muscle (P < 0.05). Fitting curves of higher acceleration factors tend to be more monoexponentially shaped. CONCLUSIONS: Simultaneous multislice acceleration provides considerable scan time reduction for upper abdomen DWI with equivalent quality of IVIM analysis compared with the standard nonaccelerated technique. Systematic discrepancies of the true Dt, D*, and Fp for SMS acquisitions need to be considered when comparing to standard DWI sequences.

In-depth analysis of interreader agreement and accuracy in categorical assessment of brown adipose tissue in (18)FDG-PET/CT.

PURPOSE: To evaluate the interreader agreement of a three-tier craniocaudal grading system for brown fat activation and investigate the accuracy of the distinction between the three grades. MATERIALS AND METHODS: After IRB approval, 340 cases were retrospectively selected from patients undergoing (18)FDG-PET/CT between 2007 and 2015 at our institution, with 85 cases in each grade and 85 controls with no active brown fat. Three readers evaluated all cases independently. Furthermore standardized uptake values (SUV) measurements were performed by two readers in a subset of 53 cases. Agreement between the readers was assessed with Cohen's Kappa (k), the concordance correlation coefficient (CCC) and the intraclass correlation coefficient (ICC). Accuracy was assessed with Bland-Altman and receiver operating characteristics (ROC) analysis. A Bonferroni-corrected two-tailed p<0.016 was considered statistically significant. RESULTS: Agreement for BAT grade was excellent by all three metrics with k=0.83-0.89, CCC=0.83-0.89 and ICC=0.91-0.94. Bland-Altman analysis revealed only slight average over- or underestimation (-0.01-0.14) with the majority of disagreements within one grade. ROC analysis yielded slightly less accurate classification between higher vs. lower grades (Area under the ROC curves 0.78-0.84 vs. 0.88-0.92) but no significant differences between readers. Agreement was also excellent for the maximum SUV and the total brown fat volume (k=0.90 and 0.94, CCC=0.93 and 0.99, ICC=0.96 and 0.99), but Bland-Altman plots revealed a tendency to underestimate activity by one of the readers. CONCLUSION: Grading the activation of brown fat by assessment of the most caudally activated depots results in excellent interreader agreement, comparable to SUV measurements.