Full-dose PET Synthesis from Low-dose PET Using High-efficiency Diffusion Denoising Probabilistic Model

To reduce the risks associated with ionizing radiation, a reduction of radiation exposure in PET imaging is needed. However, this leads to a detrimental effect on image contrast and quantification. High-quality PET images synthesized from low-dose data offer a solution to reduce radiation exposure. We introduce a diffusion-model-based approach for estimating full-dose PET images from low-dose ones: the PET Consistency Model (PET-CM) yielding synthetic quality comparable to state-of-the-art diffusion-based synthesis models, but with greater efficiency. There are two steps: a forward process that adds Gaussian noise to a full dose PET image at multiple timesteps, and a reverse diffusion process that employs a PET Shifted-window Vision Transformer (PET-VIT) network to learn the denoising procedure conditioned on the corresponding low-dose PETs. In PET-CM, the reverse process learns a consistency function for direct denoising of Gaussian noise to a clean full-dose PET. We evaluated the PET-CM in generating full-dose images using only 1/8 and 1/4 of the standard PET dose. Comparing 1/8 dose to full-dose images, PET-CM demonstrated impressive performance with normalized mean absolute error (NMAE) of 1.233+/-0.131%, peak signal-to-noise ratio (PSNR) of 33.915+/-0.933dB, structural similarity index (SSIM) of 0.964+/-0.009, and normalized cross-correlation (NCC) of 0.968+/-0.011, with an average generation time of 62 seconds per patient. This is a significant improvement compared to the state-of-the-art diffusion-based model with PET-CM reaching this result 12x faster. In the 1/4 dose to full-dose image experiments, PET-CM is also competitive, achieving an NMAE 1.058+/-0.092%, PSNR of 35.548+/-0.805dB, SSIM of 0.978+/-0.005, and NCC 0.981+/-0.007 The results indicate promising low-dose PET image quality improvements for clinical applications

Sex influences the effects of social status on socioemotional behavior and serotonin neurochemistry in rhesus monkeys

Abstract Background Despite observed sex differences in the prevalence of stress-related psychiatric conditions, most preclinical and translational studies have only included male subjects. Therefore, it has not been possible to effectively assess how sex interacts with other psychosocial risk factors to impact the etiology and maintenance of stress-related psychopathology. One psychosocial factor that interacts with sex to impact risk for stress-related behavioral and physiological deficits is social dominance. The current study was designed to assess sex differences in the effects of social status on socioemotional behavior and serotonin neurochemistry in socially housed rhesus monkeys. We hypothesized that sex and social status interact to influence socioemotional behaviors as well as serotonin 1A receptor binding potential (5HT1AR-BP) in regions of interest (ROIs) implicated in socioemotional behavior. Methods Behavioral observations were conducted in gonadally intact adult female (n = 14) and male (n = 13) rhesus monkeys. 5HT1AR-BP was assessed via positron emission tomography using 4-(2ʹ-Methoxyphenyl)-1-[2ʹ-(N-2ʺ-pyridinyl)-p[18F]fluorobenzamido]ethylpiperazine ([18F]MPPF). Results Aggression emitted was greater in dominant compared to subordinate animals, regardless of sex. Submission emitted was significantly greater in subordinate versus dominant animals and greater in females than males. Affiliative behaviors emitted were not impacted by sex, status, or their interaction. Anxiety-like behavior emitted was significantly greater in females than in males regardless of social status. Hypothalamic 5HT1AR-BP was significantly greater in females than in males, regardless of social status. 5HT1AR-BP in the dentate gyrus of the hippocampus was significantly impacted by a sex by status interaction whereby 5HT1AR-BP in the dentate gyrus was greater in dominant compared to subordinate females but was not different between dominant and subordinate males. There were no effects of sex, status, or their interaction on 5HT1AR-BP in the DRN and in the regions of the PFC studied. Conclusions These data have important implications for the treatment of stress-related behavioral health outcomes, as they suggest that sex and social status are important factors to consider in the context of serotonergic drug efficacy

Synthesis and Evaluation of Pyridyloxypyridyl Indole Carboxamides as Potential PET Imaging Agents for 5‑HT_2C Receptors

Nine pyridyloxypyridyl indole carboxamides were synthesized and displayed high affinities for 5-HT_2C receptors and high selectivity over 5-HT_2A and 5-HT_2B. Among them, 6-methyl-<i>N</i>-[6-[(2-methyl-3-pyridinyl)­oxy]-3-pyridinyl]­1<i>H</i>-indole-3-carboxamide (<b>8</b>) exhibits the highest 5-HT_2C binding affinity (<i>K</i>_i = 1.3 nM) and high selectivity over 5-HT_2A (∼1000 times) and 5-HT_2B (∼140 times). [¹¹C]<b>8</b> was synthesized by palladium-catalyzed coupling reaction between pinacolboranate <b>16</b> and [¹¹C]­CH₃I with an average radiochemical yield of 27 ± 4% (<i>n</i> = 8, decay-corrected from end of [¹¹C]­CH₃I synthesis). MicroPET imaging studies in rhesus monkeys showed regional uptake of [¹¹C]<b>8</b> in the choroid plexus, whereas the bindings in all other brain regions were low. The specific binding in the choroid plexus was confirmed by administration of a blocking dose of 0.1 mg/kg of the 5-HT_2C antagonist SB-242084

Compartmental Modeling of 11C-HOMADAM Binding to the Serotonin Transporter in the Healthy Human Brain

The novel PET radioligand 11 C- N,N -dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine ( 11 C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11 C-HOMADAM in the healthy human brain

Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction.

Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI.We studied 98 patients (49 women and 49 men) age 38-60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores.There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress.Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress

In Vitro Metabolic Stability and in Vivo Biodistribution of 3‑Methyl-4- furoxancarbaldehyde Using PET Imaging in Rats

Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that is currently difficult to treat using clinically available analgesics. Recent work suggests a progressive depletion of nitric oxide (NO) in nerve cells may be responsible for the pathobiology of PDN. The nitric oxide donor, 3-methyl-4-furoxancarbaldehyde (PRG150), has been shown to produce dose-dependent analgesia in a rat model of PDN. To gain insight into the mechanism of analgesia, methods to radiolabel PRG150 were developed to assess the in vivo biodistribution in rats. The furoxan ring was labeled with (13)N to follow any nitric oxide release and the 3-methyl substituent was labeled with (11)C to track the metabolite using PET imaging. The in vitro metabolic stability of PRG150 was assessed in rat liver microsomes and compared to in vivo metabolism of the synthesized radiotracers. PET images revealed a higher uptake of (13)N over (11)C radioactivity in the spinal cord. The differences in radioactive uptake could indicate that a NO release in the spinal cord and other components of the somatosensory nervous system may be responsible for the analgesic effects of PRG150 seen in the rat model of PDN

Mean unadjusted myocardial perfusion ischemic defect severity [raw summed difference score (SDS)] with mental stress according to five groups of progressively higher depressive symptoms using quintiles of the BDI-II total score.

<p>The error bars represent standard errors. The p-value is from a linear regression model where quintiles of the BDI-II score were modeled as an ordinal variable. There was a statistically significant progressive increase in mental stress-induced myocardial ischemia with increasing depressive symptom severity.</p