On the accuracy and reproducibility of a novel probabilistic atlas-based generation for calculation of head attenuation maps on integrated PET/MR scanners

Purpose To propose an MR-based method for generating continuous-valued head attenuation maps and to assess its accuracy and reproducibility. Demonstrating that novel MR-based photon attenuation correction methods are both accurate and reproducible is essential prior to using them routinely in research and clinical studies on integrated PET/MR scanners. Methods Continuous-valued linear attenuation coefficient maps (“μ-maps”) were generated by combining atlases that provided the prior probability of voxel positions belonging to a certain tissue class (air, soft tissue, or bone) and an MR intensity-based likelihood classifier to produce posterior probability maps of tissue classes. These probabilities were used as weights to generate the μ-maps. The accuracy of this probabilistic atlas-based continuous-valued μ-map (“PAC-map”) generation method was assessed by calculating the voxel-wise absolute relative change (RC) between the MR-based and scaled CT-based attenuation-corrected PET images. To assess reproducibility, we performed pair-wise comparisons of the RC values obtained from the PET images reconstructed using the μ-maps generated from the data acquired at three time points. Results The proposed method produced continuous-valued μ-maps that qualitatively reflected the variable anatomy in patients with brain tumor and agreed well with the scaled CT-based μ-maps. The absolute RC comparing the resulting PET volumes was 1.76 ± 2.33 %, quantitatively demonstrating that the method is accurate. Additionally, we also showed that the method is highly reproducible, the mean RC value for the PET images reconstructed using the μ-maps obtained at the three visits being 0.65 ± 0.95 %. Conclusion Accurate and highly reproducible continuous-valued head μ-maps can be generated from MR data using a probabilistic atlas-based approach.National Institutes of Health (U.S.) (grant 1R01EB014894-01A1)United States. Department of Defense (National Defense Science & Engineering Graduate Fellowship (NDSEG) Program

Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α2-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness. DOI: http://dx.doi.org/10.7554/eLife.04499.00

Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [11C]-PBR28

Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [11C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38–68 years) and ten age- and [11C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33–65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (pFWE < 0.05). Region of interest analysis revealed increased [11C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = –0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [11C]-PBR28 as a marker of treatments that target neuroinflammation

Simultaneous fMRI–PET of the opioidergic pain system in human brain

MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET data were acquired with an opioid radioligand, [(11)C]Diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo

Improved PET Data Quantification in Simultaneous PET/MR Neuroimaging

Recently, systems that integrate positron emission tomography and magnetic resonance imaging (PET/MR) have become available for clinical use. This new technology, which combines the high spatial resolution and superior soft-tissue contrast of MR with the picomolar sensitivity, quantitative capabilities, and wide array of tracers of PET, has the potential to benefit patients and provide insights that were previously unattainable in standalone systems. Simultaneous measurement of PET and MR parameters provides complementary information, allowing for a more complete assessment of disease, as well as cross validation and calibration of MR and PET measurements and techniques. To take full advantage of such a multi-modal system, accurate quantification of the PET data is necessary. Due to the low spatial resolution of PET – which can be further reduced by external factors like patient motion – and the inherent lack of anatomic detail, accurate quantification can be challenging. The simultaneously acquired MR information provides an opportunity to optimize PET quantification and analysis. In order to fully realize the benefits provided by the simultaneously acquired MR data, the MR data cannot be treated as discrete sequences, but as the continuous flow of information. This is due to differences in the time required for data collection to generate PET and MR images. This work describes the development and optimization of a pipeline for the reconstruction and analysis of PET data in a brain-dedicated prototype PET/MR system, the BrainPET (Siemens Healthcare). First, the performance of the BrainPET system was optimized for neurological imaging. MR-hardware interference and characteristics of the PET camera were quantified and a method for multimodal alignment was developed. To simplify and streamline the reconstruction and quantification process, a platform was designed which utilizes the functionality of a number of specialized brain imaging analysis software packages in an automated fashion. Second, MR-based methods addressing specific challenges to PET quantification were addressed. Simultaneously acquired structural MR data was used to correct the PET data for attenuation and partial volume effects. The use of MR data for motion correction was addressed and a unified algorithm which derives motion estimates from the PET data when MR data is unavailable was presented. Finally, the value of the optimized PET processing for neurological studies was evaluated in three instances: first an upper limit on the physiologic noise introduced by MR imaging on cerebral metabolism was estimated using PET and found to be minimal; next the benefit of MR-based motion correction and partial volume effect correction were estimated in a patient study; and lastly, a method to derive the PET radiotracer input function from the PET data using multiple MR sequences was presented.Biophysic

Discrete Bimodal Probes for Thrombus Imaging

Here we report a generalizable solid/solution-phase strategy for the synthesis of discrete bimodal fibrin-targeted imaging probes. A fibrin-specific peptide was conjugated with two distinct imaging reporters at the C- and N-termini. In vitro studies demonstrated retention of fibrin affinity and specificity. Imaging studies showed that these probes could detect fibrin over a wide range of probe concentrations by optical, magnetic resonance, and positron emission tomography imaging