Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study.

BACKGROUND AND PURPOSE: The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, the CP has been recognized as critical in modulating inflammation. MRI-measured CP enlargement has been reported in neuroinflammatory disorders like MS as well as with aging and neurodegeneration. The basis of MRI-measured CP enlargement is unknown. On the basis of tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously unmeasured CP calcification contributes to MRI-measured CP volume and may be more specifically associated with neuroinflammation. MATERIALS AND METHODS: We analyzed 60 subjects (43 healthy controls and 17 subjects with Parkinson's disease) who underwent PET/CT using 11C-PK11195, a radiotracer sensitive to the translocator protein expressed by activated microglia. Cortical inflammation was quantified as nondisplaceable binding potential. Choroid plexus calcium was measured via manual tracing on low-dose CT acquired with PET and automatically using a new CT/MRI method. Linear regression assessed the contribution of choroid plexus calcium, age, diagnosis, sex, overall volume of the choroid plexus, and ventricle volume to cortical inflammation. RESULTS: Fully automated choroid plexus calcium quantification was accurate (intraclass correlation coefficient with manual tracing = .98). Subject age and choroid plexus calcium were the only significant predictors of neuroinflammation. CONCLUSIONS: Choroid plexus calcification can be accurately and automatically quantified using low-dose CT and MRI. Choroid plexus calcification-but not choroid plexus volume-predicted cortical inflammation. Previously unmeasured choroid plexus calcium may explain recent reports of choroid plexus enlargement in human inflammatory and other diseases. Choroid plexus calcification may be a specific and relatively easily acquired biomarker for neuroinflammation and choroid plexus pathology in humans.

Resolution recovery for Compton camera using origin ensemble algorithm.

PURPOSE: Compton cameras (CCs) use electronic collimation to reconstruct the images of activity distribution. Although this approach can greatly improve imaging efficiency, due to complex geometry of the CC principle, image reconstruction with the standard iterative algorithms, such as ordered subset expectation maximization (OSEM), can be very time-consuming, even more so if resolution recovery (RR) is implemented. We have previously shown that the origin ensemble (OE) algorithm can be used for the reconstruction of the CC data. Here we propose a method of extending our OE algorithm to include RR. METHODS: To validate the proposed algorithm we used Monte Carlo simulations of a CC composed of multiple layers of pixelated CZT detectors and designed for imaging small animals. A series of CC acquisitions of small hot spheres and the Derenzo phantom placed in air were simulated. Images obtained from (a) the exact data, (b) blurred data but reconstructed without resolution recovery, and (c) blurred and reconstructed with resolution recovery were compared. Furthermore, the reconstructed contrast-to-background ratios were investigated using the phantom with nine spheres placed in a hot background. RESULTS: Our simulations demonstrate that the proposed method allows for the recovery of the resolution loss that is due to imperfect accuracy of event detection. Additionally, tests of camera sensitivity corresponding to different detector configurations demonstrate that the proposed CC design has sensitivity comparable to PET. When the same number of events were considered, the computation time per iteration increased only by a factor of 2 when OE reconstruction with the resolution recovery correction was performed relative to the original OE algorithm. We estimate that the addition of resolution recovery to the OSEM would increase reconstruction times by 2-3 orders of magnitude per iteration. CONCLUSIONS: The results of our tests demonstrate the improvement of image resolution provided by the OE reconstructions with resolution recovery. The quality of images and their contrast are similar to those obtained from the OE reconstructions from scans simulated with perfect energy and spatial resolutions.

Evaluation of Origin Ensemble algorithm for image reconstruction for pixelated solid-state detectors with large number of channels.

The Voxel Imaging PET (VIP) Pathfinder project intends to show the advantages of using pixelated solid-state technology for nuclear medicine applications. It proposes designs for Positron Emission Tomography (PET), Positron Emission Mammography (PEM) and Compton gamma camera detectors with a large number of signal channels (of the order of 106). For PET scanners, conventional algorithms like Filtered Back-Projection (FBP) and Ordered Subset Expectation Maximization (OSEM) are straightforward to use and give good results. However, FBP presents difficulties for detectors with limited angular coverage like PEM and Compton gamma cameras, whereas OSEM has an impractically large time and memory consumption for a Compton gamma camera with a large number of channels. In this article, the Origin Ensemble (OE) algorithm is evaluated as an alternative algorithm for image reconstruction. Monte Carlo simulations of the PET design are used to compare the performance of OE, FBP and OSEM in terms of the bias, variance and average mean squared error (MSE) image quality metrics. For the PEM and Compton camera designs, results obtained with OE are presented.

Pixelated CdTe detectors to overcome intrinsic limitations of crystal based positron emission mammographs.

A positron emission mammograph (PEM) is an organ dedicated positron emission tomography (PET) scanner for breast cancer detection. State-of-the-art PEMs employing scintillating crystals as detection medium can provide metabolic images of the breast with significantly higher sensitivity and specificity with respect to standard whole body PET scanners. Over the past few years, crystal PEMs have dramatically increased their importance in the diagnosis and treatment of early stage breast cancer. Nevertheless, designs based on scintillators are characterized by an intrinsic deficiency of the depth of interaction (DOI) information from relatively thick crystals constraining the size of the smallest detectable tumor. This work shows how to overcome such intrinsic limitation by substituting scintillating crystals with pixelated CdTe detectors. The proposed novel design is developed within the Voxel Imaging PET (VIP) Pathfinder project and evaluated via Monte Carlo simulation. The volumetric spatial resolution of the VIP-PEM is expected to be up to 6 times better than standard commercial devices with a point spread function of 1 mm full width at half maximum (FWHM) in all directions. Pixelated CdTe detectors can also provide an energy resolution as low as 1.5% FWHM at 511 keV for a virtually pure signal with negligible contribution from scattered events.