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Background and ObjectivesThis [18F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti–leucine-rich, glioma–inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined.MethodsFDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non–LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses.ResultsP-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non–LGI1-AE group, AD group, and NCs (all p < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84–0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non–LGI1-AE groups when compared with NCs (both p < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all p < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up.DiscussionSemiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE.Classification of EvidenceThis study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.

We have developed a new method of compensating for effects of partial volume and spillover in dual-modality imaging. The approach requires segmentation of just a few tissue types within a small VOI surrounding a lesion; the algorithm estimates simultaneously, from projection data, the activity concentration within each segmented tissue inside the VOI. Measured emission projections were fitted to the sum of resolution-blurred projections of each such tissue, scaled by its unknown activity concentration, plus a global background contribution obtained by reprojection through the reconstructed image volume outside the VOI. The method was evaluated using multiple-pinhole μSPECT data simulated for the MOBY mouse phantom containing two spherical lung tumors and one liver tumor, as well as using multiple-bead phantom data acquired on μSPECT and μCT scanners. Each VOI in the simulation study was 4.8 mm (12 voxels) cubed and, depending on location, contained up to four tissues (tumor, liver, heart, lung) with different values of relative 99mTc concentration. All tumor activity estimates achieved <3% bias after ~15 OSEM iterations (× 10 subsets), with better than 8% precision (≤25% greater than the Cramer-Rao lower bound). The projection-based fitting approach also outperformed three SUV-like metrics, one of which was corrected for count spillover. In the bead phantom experiment, the mean ± standard deviation of the bias of VOI estimates of bead concentration were 0.9 ± 9.5%, comparable to those of a perturbation geometric transfer matrix (pGTM) approach (-5.4 ± 8.6%); however, VOI estimates were more stable with increasing iteration number than pGTM estimates, even in the presence of substantial axial misalignment between μCT and μSPECT image volumes.

The microjet injector system accelerates drugs and delivers them without a needle, which is shown to overcome the weaknesses of existing jet injectors. A significant increase in the delivered dose of drugs is reported with multiple pulses of laser beam at lower laser energy than was previously used in a Nd:YAG system. The new injection scheme uses the beam wavelength best absorbable by water at a longer pulse mode for elongated microjet penetration into a skin target. A 2.9 μm Er:YAG laser at 250 μs pulse duration is used for fluorescent staining of guinea pig skin and for injection controllability study. Hydrodynamic theory confirms the nozzle exit jet velocity obtained by the present microjet system.

We demonstrate that reduced graphene oxide (rGO) coated thin aluminum film is an effective optoacoustic transmitter for generating high pressure and high frequency ultrasound previously unattainable by other techniques. The rGO layer of different thickness is deposited between a 100 nm-thick aluminum film and a glass substrate. Under a pulsed laser excitation, the transmitter generates enhanced optoacoustic pressure of 64 times the aluminum-alone transmitter. A promising optoacoustic wave generation is possible by optimizing thermoelasticity of metal film and thermal conductivity of rGO in the proposed transmitter for laser-induced ultrasound applications.

Two-component amphiphiles based on hydrogen-bonded complexes between terephthaloylbisalanine (H(2)TBA) and dodecylamine (DA) are able to self-assemble into nano- and microsized superstructures in an aqueous solvent. It is possible to modulate the morphology of these self-assembled superstructures by modifying the composition of the complexes, which can be achieved by changing the molar ratio of the two components or by changing the chirality of H(2)TBA. For example, right-handed microhelical ribbon structures were formed with L-TBA(1.0)DA(2.0), whereas in the case of rac-TBA(1.0)DA(2.0), flat ribbonlike structures were observed. Although L-TBA(1.0)DA(1.0) exhibited entangled fibrous structures, rac-TBA(1.0)DA(1.0) exhibited wire structures. Different ratios of H(2)TBA and DA were self-assembled into fiber-, wire-, and tubulelike superstructures, as well as monoclinic, columnar, and lamellar aggregation patterns. The self-assembled superstructures of TBA(x)DA(y) were significantly changed by adding metal ions. Transition metal (Cd(II), Co(II), and Zn(II)) complexes with L-TBA(x)DA(y) self-assembled into rod-, tubule-, wire-, and platelike superstructures. Metal-ion complexes with rac-TBA(x)DA(y) exhibited different superstructures. Our work suggests that it is possible to fabricate a wide variety of nano- and microsized superstructures by using two- and three-component amphiphiles.

Reactive astrogliosis is a hallmark of Alzheimer’s disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on the AD pathology, we adopted multifaceted approaches including microPET imaging, autoradiography, immunohistochemistry, metabolomics, and electrophysiology. Two AD rodent models, APP/PS1 and 5xFAD transgenic mice, one adenovirus-induced rat model of reactive astrogliosis, and post-mortem human brain tissues were used in this study. We further curated a proof-of-concept human study that included 11C-acetate and 18F-FDG PET imaging analyses along with neuropsychological assessments from 11 AD patients and 10 healthy control subjects. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. The elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-β is present. The excessive astrocytic GABA subsequently suppresses neuronal activity, which could lead to glucose uptake through decreased glucose transporter-3 in the diseased brains. We further demonstrate that 11C-acetate uptake was significantly increased in the entorhinal cortex, hippocampus and temporo-parietal neocortex of the AD patients compared to the healthy controls, while 18F-FDG uptake was significantly reduced in the same regions. Additionally, we discover a strong correlation between the patients’ cognitive function and the PET signals of both 11C-acetate and 18F-FDG. We demonstrate the potential value of PET imaging with 11C-acetate and 18F-FDG by visualizing reactive astrogliosis and the associated neuronal glucose hypometablosim for AD patients. Our findings further suggest that the acetate-boosted reactive astrocyte-neuron interaction could contribute to the cognitive decline in AD.

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