Purpose: Long-axial field-of-view PET scanners capture multi-organ tracer distribution with high sensitivity, enabling lower dose dynamic protocols and dual-tracer imaging for comprehensive disease characterization. However, reducing dose may compromise data quality and time-activity curve (TAC) fitting, leading to higher bias in kinetic parameters. Parametric imaging poses further challenges due to noise amplification in voxel-based modelling. We explore the potential of deep learning denoising (DL-DN) to improve quantification for low-dose dynamic PET. Methods: Using 16 [¹⁸F]FDG PET studies from the PennPET Explorer, we trained a DL framework on 10-min images from late-phase uptake (static data) that were sub-sampled from 1/2 to 1/300 of the counts. This model was used to denoise early-to-late dynamic frame images. Its impact on quantification was evaluated using compartmental modelling and voxel-based graphical analysis for parametric imaging for single- and dual-tracer dynamic studies with [¹⁸F]FDG and [¹⁸F]FGln at original (injected) and reduced (sub-sampled) doses. Quantification differences were evaluated for the area under the curve of TACs, K_i for [¹⁸F]FDG and V_T for [¹⁸F]FGln, and parametric images. Results: DL-DN consistently improved image quality across all dynamic frames, systematically enhancing TAC consistency and reducing tissue-dependent bias and variability in K_i and V_T down to 40 MBq doses. DL-DN preserved tumor heterogeneity in Logan V_T images and delineation of high-flux regions in Patlak K_i maps. In a /[¹⁸F]FDG dual-tracer study, bias trends aligned with single-tracer results but showed reduced accuracy for [¹⁸F]FGln in breast lesions at very low doses (4 MBq). Conclusion: This study demonstrates that applying DL-DN trained on static [¹⁸F]FDG PET images to dynamic [¹⁸F]FDG and [¹⁸F]FGln PET can permit significantly reduced doses, preserving accurate FDG K_i and FGln V_T measurements, and enhancing parametric image quality. DL-DN shows promise for improving dynamic PET quantification at reduced doses, including novel dual-tracer studies.

Functional magnetic resonance (fMR) imaging was performed in human volunteers to determine the lateral perisylvian cortical areas activated by innocuous cutaneous stimulation. Eight volunteers who underwent 53 separate experiments form the basis of this report. Eight contiguous coronal slices were obtained using echoplanar fMR imaging techniques while participants were at rest and while somatosensory activation stimuli consisting of vibration or air puffs were delivered to various body areas. The data were analyzed using Student's t-test and cluster analysis to determine significant differences between the resting and activated states. The findings were as follows: the areas in the lateral cortex activated by the stimuli were the primary sensory cortex (SI), the second somatosensory area (SII), the insula, the superior parietal lobule, and the retroinsular parietal operculum (RIPO). Somatotopy was demonstrable in SI but not in the other areas identified. There was a surprisingly low correlation between the amount of cortex activated in the various areas, which could mean separate inputs and functions for the areas identified. The highest correlation was found between activity in SII and RIPO (0.69). The authors maintain that fMR imaging can be used to identify multiple lateral somatosensory areas in humans. Somatotopy is demonstrated in SI but not in the other lateral cortical sensory areas. The correlations between the amounts of cortex activated in the different lateral sensory areas are low. Recognition of the multiple lateral sensory areas is important both for understanding sensory cortical function and for safe interpretation of studies designed to identify the central sulcus by activating SI.

Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [¹⁸F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [¹⁸F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [¹⁸F]NOS whole brain distribution volume (V_T) in PD patients compared to age-matched healthy controls (p < 0.008) via a 1-tissue compartment (TC) model. The rate constant K1 for transport from blood into tissue did not differ between groups (p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [¹⁸F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation.

A 50-year-old woman with stage IV sigmoid adenocarcinoma presented for restaging FDG PET/CT status post neoadjuvant chemotherapy/immunotherapy and diverting sigmoid colostomy. FDG PET/CT demonstrated FDG uptake in the known sigmoid mass and in abdominopelvic lymph node metastases. Bilateral, asymmetric, hypermetabolic axillary lymphadenopathy was also observed, an atypical pattern of spread for colon cancer. Further investigation revealed the patient had received both doses of COVID-19 vaccine in the 2 months prior to presentation. The authors discuss immunogenic nodal hypermetabolism following vaccination against COVID-19 and incorporating vaccination history to aid in PET/CT interpretation, especially in malignancies involving the axillae.

μ-opioid receptors (MORs) are G-coupled receptors widely expressed in the brain and body. MORs have a high affinity for both endogenous opioids such as β-endorphins and exogenous opioids such as fentanyl. They mediate pain and reward and have been implicated in the pathophysiology of opioid, cocaine, and other substance use disorders. Using an instrument with a long axial field of view and the MOR-selective radioligand [¹¹C]carfentanil, we measured the whole-body distribution of MORs in 13 healthy humans. We also examined sex differences in MOR distribution at baseline and after pretreatment with the MOR antagonist naloxone. Methods: Six female and 7 male healthy subjects underwent 2 [¹¹C]carfentanil PET imaging sessions—one at baseline and one immediately after pretreatment with the MOR antagonist naloxone (13 μg/kg). Whole-body PET imaging was performed on an instrument with a 142-cm axial bore. [¹¹C]carfentanil brain distribution volume ratios were determined using the occipital cortex and the visual cortex within it as reference regions. For peripheral organ distribution volume ratios, the descending aorta and proximal-extremity muscle (biceps/triceps) were used as reference regions. Results: Naloxone blockade reduced MOR availability by 40%–50% in the caudate, putamen, thalamus, amygdala, and ventral tegmentum, brain regions known to express high levels of MORs. Women showed greater receptor occupancy in the thalamus, amygdala, hippocampus, and frontal and temporal lobes and a greater naloxone-induced reduction in thalamic MOR availability than men (P < 0.05). For determining brain MOR availability, there was less variance in the visual cortex than in the occipital cortex reference region. For peripheral MOR determination, the descending aorta reference region showed less variance than the extremity muscle, but both showed blocking effects of naloxone. Conclusion: [¹¹C]carfentanil whole-body PET scans are useful for understanding MOR physiology under both baseline and blocking conditions. Extra–central nervous system reference regions may be useful for quantifying radiotracers when a region devoid of binding in the central nervous system is unavailable. The long axial field of view was useful for measuring changes in the short-lived radiotracer [¹¹C]carfentanil, with and without naloxone blocking. Further research is needed to evaluate the behavioral and clinical relevance of sex differences in naloxone–MOR interactions. Visual Abstract