Felmlee, Joel P.

Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

The purpose of this study is to investigate the potential of using ultrasound gel to mitigate the risks of skin burn at the insertion site during microwave ablation (MWA) using non-actively cooled applicators. Ex vivo experiments in porcine tissue were conducted using two identical MWA systems. Five MWA scenarios were tested at different applicator insertion depths with an ultrasound gel layer applied at the applicator insertion sites: 8 cm insertion depth with and without 4 cm thick gel, 10 cm insertion depth with and without 2 cm thick gel, and 12 cm insertion depth without gel (reference). In all experiments, temperature elevations at the applicator insertion site on the tissue surface were recorded using thermal sensors in all experiments during 10-min MWA. The application of ultrasound gel and increasing applicator insertion depths resulted in measurable reductions in temperature elevations at the applicator insertion sites. For an insertion depth of 8 cm, the temperature elevations were 39.9 ± 4.7°C and 23.2±6.5°C without and with gel, respectively (P < 0.001). For an insertion depth of 10 cm, the temperature elevations were 20.8 ± 1.5°C and 14.4 ± 1.5°C without and with gel, respectively (P < 0.001). The maximal temperature elevations corresponding to an 8 cm insertion depth with gel were comparable with those corresponding to a 10 cm insertion depth without gel. Similarly, the maximal temperature elevations (12.2 ± 1.8°C) corresponding to 12 cm insertion depth without gel were comparable to those corresponding to 10 cm insertion depth with gel. Applying ultrasound gel at the applicator insertion site can significantly reduce temperature elevations at the tissue surface during MWA procedures.

OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established neurosurgical treatment for the motor symptoms of Parkinson’s disease (PD). While often highly effective, DBS does not always yield optimal therapeutic outcomes, and stimulation-induced adverse effects, including paresthesia, muscle contractions, and nausea/lightheadedness, commonly occur and can limit the efficacy of stimulation. Currently, objective metrics do not exist for monitoring neural changes associated with stimulation-induced therapeutic and adverse effects. METHODS In the present study, the authors combined intraoperative functional MRI (fMRI) with STN DBS in 20 patients with PD to test the hypothesis that stimulation-induced blood oxygen level–dependent signals contained predictive information concerning the therapeutic and adverse effects of stimulation. RESULTS As expected, DBS resulted in blood oxygen level–dependent activation in myriad motor regions, including the primary motor cortex, caudate, putamen, thalamus, midbrain, and cerebellum. Across the patients, DBS-induced improvements in contralateral Unified Parkinson’s Disease Rating Scale tremor subscores correlated with activation of thalamic, brainstem, and cerebellar regions. In addition, improvements in rigidity and bradykinesia subscores correlated with activation of the primary motor cortex. Finally, activation of specific sensorimotor-related subregions correlated with the presence of DBS-induced adverse effects, including paresthesia and nausea (cerebellar cortex, sensorimotor cortex) and unwanted muscle contractions (caudate and putamen). CONCLUSIONS These results suggest that DBS-induced activation patterns revealed by fMRI contain predictive information with respect to the therapeutic and adverse effects of DBS. The use of fMRI in combination with DBS therefore may hold translational potential to guide and improve clinical stimulator optimization in patients.

AbstractPurposeAn increasing number of implantable or external devices can impact whether patients can receive radiological imaging examinations. This study examines and tests the Neulasta (pegfilgrastim) Onpro on‐body injector in multiple imaging environments.MethodsThe injector was analyzed for four imaging modalities with testing protocols and strategies developed for each modality. In x‐ray and computed tomography (CT), scans with much higher exposure than clinical protocols were performed with the device attached to an anthropomorphic phantom. The device was monitored until the completion of drug delivery. For magnetic resonance imaging (MRI), the device was assessed using a hand‐held magnet and underwent the magnetically induced displacement testing in a 1.5T clinical MRI scanner room. For ultrasound, magnetic field changes were measured around an ultrasound scanner system with three transducers.ResultsFor x‐ray and CT no sign of device error was identified during or after the high radiation exposure scans. Drug delivery was completed at expected timing with expected volume. For MRI the device showed significant attractive force towards the hand‐held magnet and a 50‐degree deflection angle at 50 cm from the opening of the scanner bore. No further assessment from the gradient or radiofrequency field was deemed necessary. For ultrasound the maximum magnetic field change from baseline was measured to be +11.7 μT in comparison to +74.2 μT at 4 inches from a working microwave.ConclusionsNo device performance issue was identified under the extreme test conditions in x‐ray or CT. The device was found to be MR Unsafe. Magnetic field changes around an ultrasound system met the limitation set by manufacture. Patient ultrasound scanning is considered safe as long as the transducers do not inadvertently loosen the device.

PurposeA 7T magnetic resonance thermometry (MRT) technique was developed to validate the conversion factor between the system‐measured transmitted radiofrequency (RF) power into a home‐built RF wrist coil with the system‐predicted SAR value. The conversion factor for a new RF coil developed for ultra high magnetic field MRI systems is used to ensure that regulatory limits on RF energy deposition in tissue, specifically the local 10g‐averaged specific absorption rate (SAR10g), are not exceeded. MRT can be used to validate this factor by ensuring that MRT‐measured SAR values do not exceed those predicted by the system.MethodsA 14‐cm diameter high‐pass birdcage RF coil was built to image the wrist at 7T. A high spatial and temporal resolution dual‐echo gradient echo MRT technique, incorporating quasi‐simultaneous RF‐induced heating and temperature change measurements using the proton resonance frequency method, was developed. The technique allowed for high‐temperature resolution measurements (~±0.1°C) to be performed every 20 s over a 4‐min heating period, with high spatial resolution (2.56 mm3 voxel size) and avoiding phase discontinuities arising from severe magnetic susceptibility‐induced B0 inhomogeneities. Magnetic resonance thermometry was performed on a phantom made from polyvinylpyrrolidone to mimic the dielectric properties of muscle tissue at 297.2 MHz. Temperature changes measured with MRT and four fiber optic temperature sensors embedded in the phantom were compared. Electromagnetic simulations of the coil and phantom were developed and validated via comparison of simulated and measured B1+ maps in the phantom. The position of maximum SAR within the coil was determined from simulations, and MRT was performed within a wrist‐sized piece of meat positioned at that SAR hotspot location. MRT‐measured and system‐predicted SAR values for the phantom and meat were compared.ResultsTemperature change measurements from MRT matched closely to those from the fiber optic temperature sensors. The simulations were validated via close correlation between the simulated and MRT‐measured B1+ and SAR maps. Using a coil conversion factor of 2 kg−1, MRT‐measured point‐SAR values did not exceed the system‐predicted SAR10g in either the uniform phantom or in the piece of meat mimicking the wrist located at the SAR hotspot location.ConclusionsA highly accurate MRT technique with high spatial and temporal resolution was developed. This technique can be used to ensure that system‐predicted SAR values are not exceeded in practice, thereby providing independent validation of SAR levels delivered by a newly built RF wrist coil. The MRT technique is readily generalizable to perform safety evaluations for other RF coils at 7T.

AbstractBackgroundMagnetic resonance imaging (MRI) in patients with legacy cardiovascular implantable electronic devices (CIEDs) in situ is likely underutilized. We hypothesized the clinical benefit of MRI would outweigh the risks in legacy CIED patients.MethodsThis is a single‐center retrospective study that evaluated and classified the utility of MRI using a prospectively maintained database. The outcomes were classified as aiding in diagnosis, treatment, or both for the patients attributable to the MRI. We then assessed the incidence of adverse effects (AE) when the MRI was performed.ResultsIn 668, MRIs performed on 479 patients, only 13 (1.9%) MRIs did not aid in the diagnosis or treatment of the patient. Power‐on reset events without clinical sequelae in three scans (0.45%) were the only AE. The probability of an adverse event happening without any benefit from the MRI scan was 1.1 × 10−4. A maximum benefit in diagnosis using MRI was obtained in ruling out space‐occupying lesions (121/185 scans, 65.4%). Scans performed in patients for elucidating answers to queries in treatment were most frequently done for disease staging at long term follow‐up (167/470 scans, 35.5%). Conservative treatment (184/470 scans, 39%) followed by medication changes (153/470 scans, 28.7%) were the most common treatment decisions made.ConclusionsThe utility of MRI in patients with non‐MRI‐conditional CIEDs far outweighs the risk of adverse events when imaging is done in the context of a multidisciplinary program that oversees patient safety.

When a breast lesion is seen on only magnetic resonance imaging (MRI) and needs to be excised, pre-operative MRI-guided radioactive seed localization (RSL) is preferred. However, MRI safety and radiation safety issues associated with the inability to recover a potentially lost seed in the MRI scanner room (Zone IV) have precluded this in the past. This manuscript provides a protocol for MRI-guided RSLs that meets MRI safety and radiation safety criteria established by the American College of Radiology and the Nuclear Regulatory Commission. To the authors’ best knowledge, this has never been published in the literature. The complete protocol is provided.

Abstract Recent guideline statements approve the performance of magnetic resonance imaging (MRI) in patients with non-conditional cardiac implantable electronic devices (CIEDs) under certain closely monitored conditions. Data from current registries may have lower power to discern changes that may occur in the CIED after the MRI. Objective We aimed to systematically review the literature to identify the adverse events and significance of changes in device function associated with performing MRI in patients with CIEDs Methods A comprehensive literature search of the databases was performed between 1980- 2017. Two independent reviewers selected studies and extracted data. A random-effects model was used for meta-analysis. Results A total of 7,422 patients underwent 8,865 MRI studies. No death occurred post MRI. Clinical adverse events were extremely rare (mostly less than 1%) and are summarized in Table 1. No significant changes in the pooled mean effect size estimate was noted for the changes in the lead parameters (pacing threshold, sensing and impedance) Binary outcomes post magnetic resonance imaging in patients with non-conditional cardiac implantable electronic devices Outcome Sample size Number of patients Rate SE LL of CI UL of CI Death 7401 0 0 0 0 0 Atrial arrhythmia 7173 10 0.001 0.0004 0.0007 0.0024 Ventricular arrhythmia 7371 9 0.0012 0.0004 0.0006 0.0022 Oversensing 4981 17 0.0034 0.0008 0.0020 0.0053 Inhibition of pacing 7371 6 0.0008 0.0003 0.0003 0.0016 Lead Failure/Generator Failure 7475/7475 2/8 0.0002/0.0011 0.0001/0.0004 0.0001/0.0005 0.0009/0.002 Power on Reset 1388 105 0.0131 0.0014 0.0107 0.0161 Did not complete scan 6851 13 0.0019 0.0005 0.0011 0.0031 Chest pain 7080 11 0.0021 0.0004 0.0008 0.0027. Lead threshold rise (>0.5v/>50%-A/V) 5076/6246 12/16 0.0024/0.0026 0.0007/0.0006 0.0013/0.0015 0.0040/0.0041 Change in Battery voltage >0.04V 7132 42 0.0061 0.0009 0.0043 0.0079 Sensing decrease >50%-A/V 5087/5834 17/9 0.0033/0.0015 0.0008/0.0005 0.0020/0.0008 0.0052/0.0028 Impedance changes >50ohms/>50% 5810 22 0.0038 0.0008 0.0024 0.0057 Rise in cardiac enzymes 1703 26 0.0152 0.0030 0.0102 0.0219 A, atrial; V, ventricular; SE, standard Error; LL, lower limit; UL, upper limit; CI, Confidence intervals. Conclusions MRI in patients with non-conditional CIEDs can be performed with high degree of safety and low rate of clinical events when performed under standardized protocols Acknowledgement/Funding None

Objectives The aim of this work was to devise mitigation strategies for addressing a range of image artifacts on a clinical 7 T magnetic resonance imaging scanner using the regulatory-approved single-channel radiofrequency transmit mode and vendor-supplied radiofrequency coils to facilitate clinical scanning within reasonable scan times. Materials and Methods Optimized imaging sequence protocols were developed for routine musculoskeletal knee and neurological imaging. Sources of severe image nonuniformities were identified, and mitigation strategies were devised. A range of custom-made high permittivity dielectric pads were used to compensate for B1 + and B1 − inhomogeneities, and also for magnetic susceptibility-induced signal dropouts particularly in the basal regions of the temporal lobes and in the cerebellum. Results Significant improvements in image uniformity were obtained using dielectric pads in the knee and brain. A combination of small voxels, reduced field of view B0 shimming, and high in-plane parallel imaging factors helped to minimize signal loss in areas of high susceptibility-induced field distortions. The high inherent signal-to-noise ratio at 7 T allowed for high receiver bandwidths and thin slices to minimize chemical shift artifacts. Intermittent artifacts due to radiofrequency inversion pulse limitations (power, bandwidth) were minimized with dielectric pads. A patient with 2 implanted metallic cranial fixation devices located within the radiofrequency transmit field was successfully imaged, with minimal image geometric distortions. Conclusions Challenges relating to severe image artifacts at 7 T using single-channel radiofrequency transmit functionality in the knee and brain were overcome using the approaches described in this article. The resultant high diagnostic image quality paves the way for incorporation of this technology into the routine clinical workflow. Further developmental efforts are required to expand the range of applications to other anatomical areas, and to expand the evidence- and knowledge-base relating to the safety of scanning patients with implanted metallic devices.