Evaluation of a High-Sensitivity Organ-Targeted PET Camera.

The aim of this study is to evaluate the performance of the Radialis organ-targeted positron emission tomography (PET) Camera with standardized tests and through assessment of clinical-imaging results. Sensitivity, count-rate performance, and spatial resolution were evaluated according to the National Electrical Manufacturers Association (NEMA) NU-4 standards, with necessary modifications to accommodate the planar detector design. The detectability of small objects was shown with micro hotspot phantom images. The clinical performance of the camera was also demonstrated through breast cancer images acquired with varying injected doses of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) and qualitatively compared with sample digital full-field mammography, magnetic resonance imaging (MRI), and whole-body (WB) PET images. Micro hotspot phantom sources were visualized down to 1.35 mm-diameter rods. Spatial resolution was calculated to be 2.3 ± 0.1 mm for the in-plane resolution and 6.8 ± 0.1 mm for the cross-plane resolution using maximum likelihood expectation maximization (MLEM) reconstruction. The system peak noise equivalent count rate was 17.8 kcps at a 18F-FDG concentration of 10.5 kBq/mL. System scatter fraction was 24%. The overall efficiency at the peak noise equivalent count rate was 5400 cps/MBq. The maximum axial sensitivity achieved was 3.5%, with an average system sensitivity of 2.4%. Selected results from clinical trials demonstrate capability of imaging lesions at the chest wall and identifying false-negative X-ray findings and false-positive MRI findings, even at up to a 10-fold dose reduction in comparison with standard 18F-FDG doses (i.e., at 37 MBq or 1 mCi). The evaluation of the organ-targeted Radialis PET Camera indicates that it is a promising technology for high-image-quality, low-dose PET imaging. High-efficiency radiotracer detection also opens an opportunity to reduce administered doses of radiopharmaceuticals and, therefore, patient exposure to radiation.

Image quality evaluation for a clinical organ-targeted PET camera.

Introduction: A newly developed clinical organ-targeted Positron Emission Tomography (PET) system (also known as Radialis PET) is tested with a set of standardized and custom tests previously used to evaluate the performance of Positron Emission Mammography (PEM) systems. Methods: Imaging characteristics impacting standardized uptake value (SUV) and detectability of small lesions, namely spatial resolution, linearity, uniformity, and recovery coefficients, are evaluated. Results: In-plane spatial resolution was measured as 2.3 mm ± 0.1 mm, spatial accuracy was 0.1 mm, and uniformity measured with flood field and NEMA NU-4 phantom was 11.7% and 8.3% respectively. Selected clinical images are provided as reference to the imaging capabilities under different clinical conditions such as reduced activity of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) and time-delayed acquisitions. SUV measurements were performed for selected clinical acquisitions to demonstrate a capability for quantitative image assessment of different types of cancer including for invasive lobular carcinoma with comparatively low metabolic activity. Quantitative imaging performance assessment with phantoms demonstrates improved contrast recovery and spill-over ratio for this PET technology when compared to other commercial organ-dedicated PET systems with similar spatial resolution. Recovery coefficients were measured to be 0.21 for the 1 mm hot rod and up to 0.89 for the 5 mm hot rod of NEMA NU-4 Image Quality phantom. Discussion: Demonstrated ability to accurately reconstruct activity in tumors as small as 5 mm suggests that the Radialis PET technology may be well suited for emerging clinical applications such as image guided assessment of response to neoadjuvant systemic treatment (NST) in lesions smaller than 2 cm. Also, our results suggest that, while spatial resolution greatly influences the partial volume effect which degrades contrast recovery, optimized count rate performance and image reconstruction workflow may improve recovery coefficients for systems with comparable spatial resolution. We emphasize that recovery coefficient should be considered as a primary performance metric when a PET system is used for accurate lesion size or radiotracer uptake assessments.

Breast Cancer Detection Using a Low-Dose Positron Emission Digital Mammography System.

Purpose To investigate the feasibility of low-dose positron emission mammography (PEM) concurrently to MRI to identify breast cancer and determine its local extent. Materials and Methods In this research ethics board-approved prospective study, participants newly diagnosed with breast cancer with concurrent breast MRI acquisitions were assigned independently of breast density, tumor size, and histopathologic cancer subtype to undergo low-dose PEM with up to 185 MBq of fluorine 18-labeled fluorodeoxyglucose (18F-FDG). Two breast radiologists, unaware of the cancer location, reviewed PEM images taken 1 and 4 hours following 18F-FDG injection. Findings were correlated with histopathologic results. Detection accuracy and participant details were examined using logistic regression and summary statistics, and a comparative analysis assessed the efficacy of PEM and MRI additional lesions detection (ClinicalTrials.gov: NCT03520218). Results Twenty-five female participants (median age, 52 years; range, 32-85 years) comprised the cohort. Twenty-four of 25 (96%) cancers (19 invasive cancers and five in situ diseases) were identified with PEM from 100 sets of bilateral images, showcasing comparable performance even after 3 hours of radiotracer uptake. The median invasive cancer size was 31 mm (range, 10-120). Three additional in situ grade 2 lesions were missed at PEM. While not significant, PEM detected fewer false-positive additional lesions compared with MRI (one of six [16%] vs eight of 13 [62%]; P = .14). Conclusion This study suggests the feasibility of a low-dose PEM system in helping to detect invasive breast cancer. Though large-scale clinical trials are essential to confirm these preliminary results, this study underscores the potential of this low-dose PEM system as a promising imaging tool in breast cancer diagnosis. ClinicalTrials.gov registration no. NCT03520218 Keywords: Positron Emission Digital Mammography, Invasive Breast Cancer, Oncology, MRI Supplemental material is available for this article. © RSNA, 2024 See also commentary by Barreto and Rapelyea in this issue.

Preclinical in vivo longitudinal assessment of KG207-M as a disease-modifying Alzheimer's disease therapeutic.

In vivo biomarker abnormalities provide measures to monitor therapeutic interventions targeting amyloid-ß pathology as well as its effects on downstream processes associated with Alzheimer's disease pathophysiology. Here, we applied an in vivo longitudinal study design combined with imaging and cerebrospinal fluid biomarkers, mirroring those used in human clinical trials to assess the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment in the McGill-R-Thy1-APP transgenic rat model. The bi-functional fusion protein consisted of a blood-brain barrier crossing single domain antibody (FC5) fused to an amyloid-ß oligomer-binding peptide (ABP) via Fc fragment of mouse IgG (FC5-mFc2a-ABP). A five-week treatment with FC5-mFc2a-ABP (loading dose of 30 mg/Kg/iv followed by 15 mg/Kg/week/iv for four weeks) substantially reduced brain amyloid-ß levels as measured by positron emission tomography and increased the cerebrospinal fluid amyloid-ß42/40 ratio. In addition, the 5-week treatment rectified the cerebrospinal fluid neurofilament light chain concentrations, resting-state functional connectivity, and hippocampal atrophy measured using magnetic resonance imaging. Finally, FC5-mFc2a-ABP (referred to as KG207-M) treatment did not induce amyloid-related imaging abnormalities such as microhemorrhage. Together, this study demonstrates the translational values of the designed preclinical studies for the assessment of novel therapies based on the clinical biomarkers providing tangible metrics for designing early-stage clinical trials.

Improved discrimination of visual stimuli following repetitive transcranial magnetic stimulation.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a "virtual lesion" in stimulated brain regions, with correspondingly diminished behavioral performance. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of rTMS to visual cortex on subjects' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz) stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task. CONCLUSIONS/SIGNIFICANCE: Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception.