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Accurately identifying the peripheral pain generator in patients with chronic pain remains a major challenge for modern medicine. Millions of patients around the world suffer endlessly from difficult-to-manage debilitating pain because of very limited diagnostic tests and a paucity of pain therapies. To help these patients, we have developed a novel clinical molecular imaging approach, and, in its early stages, it has been shown to accurately identify the exact site of pain generation using an imaging biomarker for the sigma-1 receptor and positron emission tomography/magnetic resonance imaging. We hope the description of the work in this article can help others begin their own pain imaging programs at their respective institutions.

Objective The goal of this study is to demonstrate the feasibility of simultaneous [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) for noninvasive visualization of muscular, neurovascular, and skin changes secondary to complex regional pain syndrome (CRPS). Subjects Seven adult patients with CRPS of the foot and seven healthy adult controls participated in our [18F]FDG PET/MRI study. Methods All participants received whole-body PET/MRI scans 1 hour after the injection of 370MBq [18F]FDG. Resulting PET/MRI images were reviewed by two radiologists. Metabolic and anatomic abnormalities identified, were grouped into muscular, neurovascular, and skin lesions. The [18F]FDG uptake of each lesion was compared with that of corresponding areas in controls using a Mann-Whitney U -test. Results On PET images, muscular abnormalities were found in five patients, neurovascular abnormalities in four patients, and skin abnormalities in two patients. However, on MRI images, no muscular abnormalities were detected. Neurovascular abnormalities and skin abnormalities in the affected limb were identified on MRI in one and two patients, respectively. The difference in [18F]FDG uptake between the patients and the controls was significant in muscle (P  = .018) and neurovascular bundle (P  = .0005). Conclusions The increased uptake of [18F]FDG in the symptomatic areas likely reflects the increased metabolism due to the inflammatory response causing pain. Therefore, our approach combining metabolic [18F]FDG PET and anatomic MR imaging may offer noninvasive monitoring of the distribution and progression of inflammatory changes associated with CRPS. [ABSTRACT FROM AUTHOR]

Purpose: To improve the homogeneity and consistency of apparent diffusion coefficient (ADC) estimates in cartilage from the double‐echo in steady‐state (DESS) sequence by applying SNR‐weighted regularization during post‐processing. Methods: An estimation method that linearizes ADC estimates from DESS is used in conjunction with a smoothness constraint to suppress noise‐induced variation in ADC estimates. Simulations, phantom scans, and in vivo scans are used to demonstrate how the method reduces ADC variability. Conventional diffusion‐weighted echo‐planar imaging (DW EPI) maps are acquired for comparison of mean and standard deviation (SD) of the ADC estimate. Results: Simulations and phantom scans demonstrated that the SNR‐weighted regularization can produce homogenous ADC maps at varying levels of SNR, whereas non‐regularized maps only estimate ADC accurately at high SNR levels. The in vivo maps showed that the SNR‐weighted regularization produced ADC maps with similar heterogeneity to maps produced with standard DW EPI, but without the distortion of such reference scans. Conclusion: A linear approximation of a simplified model of the relationship between DESS signals allows for fast SNR‐weighted regularization of ADC maps that reduces estimation error in relatively short T2 tissue such as cartilage. [ABSTRACT FROM AUTHOR]

Purpose To develop a fast 2D method for MRI near metal with reduced B0 in-plane and through-slice artifacts. Methods Multi-spectral imaging (MSI) approaches reduce artifacts in MR images near metal, but require 3D imaging of multiple excited volumes regardless of imaging geometry or artifact severity. The proposed 2D MSI method rapidly excites a limited slice and spectral region using gradient reversal between excitation and refocusing pulses, then uses standard 2D imaging, with the process repeating to cover multiple spectral offsets that are combined as in other MSI techniques. 2D MSI was implemented in a spin-echo-train sequence and validated in phantoms and in vivo by comparing it with standard spin-echo imaging and existing MSI techniques. Results 2D MSI images for each spatial-spectral region follow isocontours of the dipole-like B0 field variation, and thus frequency variation, near metal devices. Artifact correction in phantoms and human subjects with metal is comparable to 3D MSI methods, and superior to standard spin-echo techniques. Scan times are reduced compared with 3D MSI methods in cases where a limited number of slices are needed, though signal-to-noise ratio is also reduced as expected. Conclusion 2D MSI offers a fast and flexible alternative to 3D MSI for artifact reduction near metal. Magn Reson Med 79:968-973, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose: Sigma-1 receptors (S1Rs) play an important role in many neurological disorders. Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) with S1R radioligands may provide valuable information for diagnosing and guiding treatment for these diseases. Our previously reported S1R radioligand, [18F]FTC-146, demonstrated high affinity for the S1R (K i = 0.0025 nM) and excellent selectivity for the S1R over the sigma-2 receptor (S2Rs; K i = 364 nM) across several species (from mouse to non-human primate). Herein, we report the clinical-grade radiochemistry filed with exploratory Investigational New Drug (eIND) and first-in-human PET/MRI evaluation of [18F]FTC-146.Procedures: [18F]FTC-146 is prepared via a direct [18F] fluoride nucleophilic radiolabeling reaction and formulated in 0.9 % NaCl containing no more than 10 % ethanol through sterile filtration. Quality control (QC) was performed based on USP 823 before doses were released for clinical use. The safety and whole body biodistribution of [18F]FTC-146 were evaluated using a simultaneous PET/MR scanner in two representative healthy human subjects.Results: [18F]FTC-146 was synthesized with a radiochemical yield of 3.3 ± 0.7 % and specific radioactivity of 8.3 ± 3.3 Ci/μmol (n = 10, decay corrected to EOB). Both radiochemical and chemical purities were >95 %; the prepared doses were stable for 4 h at ambient temperature. All QC test results met specified clinical criteria. The in vivo PET/MRI investigations showed that [18F]FTC-146 rapidly crossed the blood brain barrier and accumulated in S1R-rich regions of the brain. There were also radioactivity distributed in the peripheral organs, i.e., the lungs, spleen, pancreas, and thyroid. Furthermore, insignificant uptake of [18F]FTC-146 was observed in cortical bone and muscle.Conclusion: A reliable and automated radiosynthesis for providing routine clinical-grade [18F]FTC-146 for human studies was established in a modified GE TRACERlab FXFN. PET/MRI demonstrated the initial tracer biodistribution in humans, and clinical studies investigating different S1R-related diseases are in progress. [ABSTRACT FROM AUTHOR]

Purpose To estimate the susceptibility and the geometry of metallic implants from multispectral imaging (MSI) information, to separate the metal implant region from the surrounding signal loss region. Theory and Methods The susceptibility map of signal-void regions is estimated from MSI B0 field maps using total variation (TV) regularized inversion. Voxels with susceptibility estimates above a predetermined threshold are identified as metal. The accuracy of the estimated susceptibility and implant geometry was evaluated in simulations, phantom, and in vivo experiments. Results The proposed method provided more accurate susceptibility estimation compared with a previous method without TV regularization, in both simulations and phantom experiments. In the phantom experiment where the actual implant was 40% of the signal-void region, the mean estimated susceptibility was close to the susceptibility in literature, and the precision and recall of the estimated geometry was 85% and 93%. In vivo studies in subjects with hip implants also demonstrated that the proposed method can distinguish implants from surrounding low-signal tissues, such as cortical bone. Conclusion The proposed method can improve the delineation of metallic implant geometry by distinguishing metal voxels from artificial signal voids and low-signal tissues by estimating the susceptibility maps. Magn Reson Med 77:2402-2413, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]