F-FTC-146 in humans.
Journal of nuclear medicine
The purpose of this study is to assess safety, biodistribution and radiation dosimetry in humans for the highly selective sigma-1 receptor (S1R) positron emission tomography (PET) agent (18)F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ((18)F-FTC-146). Methods: Ten healthy volunteers (HV; five female, five male; age: 34.3 ± 6.5 years) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/magnetic resonance imaging (PET/MRI) examinations were acquired for up to three hours after injection (357.2 ± 48.8 MBq). Blood samples were collected and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions-of-interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry was estimated using PMOD 3.7 and Organ Linear Internal Dose Assessment (OLINDA). Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to (18)F-FTC-146 were reported. High accumulation of (18)F-FTC-146 was observed in S1R dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose (ED) of (18)F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range: 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade (18)F-FTC-146 were successful. Injection of (18)F-FTC-146 is safe, and absorbed doses are acceptable. The potential of (18)F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.
View details for DOI 10.2967/jnumed.117.192641
View details for PubMedID 28572487
- Metallic Implant Geometry and Susceptibility Estimation Using Multispectral B-0 Field Maps MAGNETIC RESONANCE IN MEDICINE 2017; 77 (6): 2402-2413
2D multi-spectral imaging for fast MRI near metal.
Magnetic resonance in medicine
To develop a fast 2D method for MRI near metal with reduced B0 in-plane and through-slice artifacts.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.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.2D MSI offers a fast and flexible alternative to 3D MSI for artifact reduction near metal. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
View details for DOI 10.1002/mrm.26724
View details for PubMedID 28444805
Molecular imaging and biology
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, [(18)F]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 [(18)F]FTC-146.[(18)F]FTC-146 is prepared via a direct [(18)F] 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 [(18)F]FTC-146 were evaluated using a simultaneous PET/MR scanner in two representative healthy human subjects.[(18)F]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 [(18)F]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 [(18)F]FTC-146 was observed in cortical bone and muscle.A reliable and automated radiosynthesis for providing routine clinical-grade [(18)F]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.
View details for DOI 10.1007/s11307-017-1064-z
View details for PubMedID 28280965
Feasibility of 7T MRI for Imaging Fascicular Structures of Peripheral Nerves.
Muscle & nerve
Evaluation of the nerve fascicular structure can be useful in diagnosing nerve damage, but it is a very challenging task with 3T MRI due to limited resolution. In this pilot study, we present the feasibility of high-resolution 7T MRI for examining the nerve fascicular structure.A 3D gradient-spoiled sequence was used for imaging peripheral nerves in extremities. Images acquired with different in-plane resolutions (0.42 x 0.42mm vs. 0.12 x 0.12mm), and different main field strengths (7T vs. 3T) were compared.The individual nerve fascicles were identified at 0.12 x 0.12mm resolution in both field strengths, but not at 0.42 x 0.42mm resolution. The fascicular structure was more sharply depicted in 7T images than in 3T images.High-resolution 3D imaging with 7T MRI demonstrated feasibility in imaging nerve fascicular structures. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/mus.26035
View details for PubMedID 29211916
18F-FDG PET/MRI in Chronic Sciatica: Early Results Revealing Spinal and Non-spinal Abnormalities.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Chronic sciatica is a major cause of disability worldwide, but accurate diagnosis of the offending pathology remains challenging. In this report, the feasibility of a fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) approach for improved diagnosis of chronic sciatica is presented. Methods:18F-FDG PET/MRI was performed on 9 chronic sciatica patients and 5 healthy volunteers. Region-of-interest analysis using maximum standardized uptake values (SUVmax) was performed, and 18F-FDG uptake in lesions was compared with the corresponding areas in healthy controls. Results: Significantly increased 18F-FDG uptake was observed in detected lesions of all patients, which was correlated with pain symptoms. 18F-FDG-avid lesions were not only found in impinged spinal nerves, but were also associated with non-spinal causes, such as a facet joint degeneration, pars defect, or a presumed scar neuroma. Conclusion: The feasibility of 18F-FDG PET/MRI for diagnosing pain generators in chronic sciatica has been demonstrated, revealing various possible etiologies.
View details for DOI 10.2967/jnumed.117.198259
View details for PubMedID 29097408
Prolongation of ERP latency and reaction time (RT) in simultaneous EEG/fMRI data acquisition
JOURNAL OF NEUROSCIENCE METHODS
2016; 268: 78-86
Recording EEG and fMRI data simultaneously inside a fully-operating scanner has been recognized as a novel approach in human brain research. Studies have demonstrated high concordance between the EEG signals and hemodynamic response. However, a few studies reported altered cognitive process inside the fMRI scanner such as delayed reaction time (RT) and reduced and/or delayed N100 and P300 event-related brain potential (ERP) components.The present study investigated the influence of electromagnetic field (static magnetic field, radio frequency (RF) pulse, and gradient switching) and experimental environment on posterior N100 and P300 ERP components in four different settings with six healthy subjects using a visual oddball task: (1) classic fMRI acquisition inside the scanner (e.g., supine position, mirror glasses for stimulus presentation), (2) standard behavioral experiment outside the scanner (e.g., seated position, keyboard response), (3) controlled fMRI acquisition inside the scanner (e.g., organic light-emitting diode (OLED) goggles for stimulus presentation) inside; and (4) modified behavioral experiment outside the scanner (e.g., supine position, OLED goggles).The study findings indicated that the experimental environment in simultaneous EEG/fMRI acquisition could substantially delay N1P, P300 latency, and RT inside the scanner, and was associated with a reduced N1P amplitude.There was no effect of electromagnetic field in the prolongation of RT, N1P and P300 latency inside the scanner. N1P, but not P300, latency was sensitive to stimulus presentation method inside the scanner.Future simultaneous EEG/fMRI data collection should consider experimental environment in both design and analysis.
View details for DOI 10.1016/j.jneumeth.2016.05.011
View details for Web of Science ID 000379104400010
View details for PubMedID 27172845
MR thermometry near metallic devices using multispectral imaging.
Magnetic resonance in medicine
The lack of a technique for MR thermometry near metal excludes a growing patient population from promising treatments such as MR-guided focused ultrasound therapy. Here we explore the feasibility of multispectral imaging (MSI) for noninvasive temperature measurement in the presence of strong field inhomogeneities by exploiting the temperature dependency of the T1 relaxation time.A two-dimensional inversion-recovery-prepared MSI pulse sequence (2DMSI) was implemented for artifact-reduced T1 mapping near metal. A series of T1 maps was acquired in a metallic implant phantom while increasing the phantom temperature. The measured change in T1 was analyzed with respect to the phantom temperature. For comparison, proton resonance frequency shift (PRFS) thermometry was performed.2DMSI achieved artifact-reduced, single-slice T1 mapping in the presence of strong off-resonance with a spatial resolution of 1.9 mm in-plane and a temporal resolution of 5 min. The maps enabled temperature measurements over a range of 30°C with an uncertainty below 1.4°C. The quality of the resulting temperature maps was independent of the distance from the metal, whereas the PRFS-based temperature measurements were increasingly impaired with increasing off-resonance.We demonstrated the ability to noninvasively measure temperature near metal using MSI and the T1 temperature sensitivity. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.
View details for DOI 10.1002/mrm.26203
View details for PubMedID 26991803
Small-tip fast recovery imaging using non-slice-selective tailored tip-up pulses and radiofrequency-spoiling
MAGNETIC RESONANCE IN MEDICINE
2013; 69 (3): 657-666
Small-tip fast recovery (STFR) imaging is a new steady-state imaging sequence that is a potential alternative to balanced steady-state free precession. Under ideal imaging conditions, STFR may provide comparable signal-to-noise ratio and image contrast as balanced steady-state free precession, but without signal variations due to resonance offset. STFR relies on a tailored "tip-up," or "fast recovery," radiofrequency pulse to align the spins with the longitudinal axis after each data readout segment. The design of the tip-up pulse is based on the acquisition of a separate off-resonance (B0) map. Unfortunately, the design of fast (a few ms) slice- or slab-selective radiofrequency pulses that accurately tailor the excitation pattern to the local B0 inhomogeneity over the entire imaging volume remains a challenging and unsolved problem. We introduce a novel implementation of STFR imaging based on "non-slice-selective" tip-up pulses, which simplifies the radiofrequency pulse design problem significantly. Out-of-slice magnetization pathways are suppressed using radiofrequency-spoiling. Brain images obtained with this technique show excellent gray/white matter contrast, and point to the possibility of rapid steady-state T(2)/T(1) -weighted imaging with intrinsic suppression of cerebrospinal fluid, through-plane vessel signal, and off-resonance artifacts. In the future, we expect STFR imaging to benefit significantly from parallel excitation hardware and high-order gradient shim systems.
View details for DOI 10.1002/mrm.24289
View details for Web of Science ID 000315331300006
View details for PubMedID 22511367
View details for PubMedCentralID PMC3408566
Fast joint design method for parallel excitation radiofrequency pulse and gradient waveforms considering off-resonance
MAGNETIC RESONANCE IN MEDICINE
2012; 68 (1): 278-285
A fast parallel excitation pulse design algorithm to select and to order phase-encoding (PE) locations (also known as "spokes") of an Echo-Volumar excitation k-space trajectory considering B(0) field inhomogeneity is presented. Recently, other groups have conducted research to choose optimal PE locations, but the potential benefit of considering B(0) field inhomogeneity during PE location selection or their ordering has not been fully investigated. This article introduces a novel fast greedy algorithm to determine PE locations and their order that takes into account the off-resonance effects. Computer simulations of the proposed algorithm for B(1) field inhomogeneity correction demonstrate that it not only improves excitation accuracy but also provides an effective ordering of the PE locations.
View details for DOI 10.1002/mrm.24311
View details for Web of Science ID 000305119100029
View details for PubMedID 22555857
View details for PubMedCentralID PMC3939078
Spectral-Spatial Pulse Design for Through-Plane Phase Precompensatory Slice Selection in T-2(star)-Weighted Functional MRI
MAGNETIC RESONANCE IN MEDICINE
2009; 61 (5): 1137-1147
T(2)*-weighted functional MR images suffer from signal loss artifacts caused by the magnetic susceptibility differences between air cavities and brain tissues. We propose a novel spectral-spatial pulse design that is slice-selective and capable of mitigating the signal loss. The two-dimensional spectral-spatial pulses create precompensatory phase variations that counteract through-plane dephasing, relying on the assumption that resonance frequency offset and through-plane field gradient are spatially correlated. The pulses can be precomputed before functional MRI experiments and used repeatedly for different slices in different subjects. Experiments with human subjects showed that the pulses were effective in slice selection and loss mitigation at different brain regions.
View details for DOI 10.1002/mrm.21938
View details for Web of Science ID 000265566000017
View details for PubMedID 19267346
View details for PubMedCentralID PMC2856348